A new strategy to sustained release of ocular drugs by one-step drug-loaded microcapsule manufacturing in hydrogel punctal plugs.

PubMed

Xie, Jiajun; Wang, Changjun; Ning, Qingyao; Gao, Qi; Gao, Changyou; Gou, Zhongru; Ye, Juan

2017-11-01

To design an injectable hyaluronate (HA)-based hydrogel system that contains drug-loaded microcapsules as resorbable plugs to deliver ocular drugs. In-situ drug-loaded, core-shell-structured chitosan (CS)@HA microcapsules were fabricated via HA hydrosol collecting in electrospun bead-rich CS fibers under continuous stirring. An injectable and cytocompatible hydrogel system with different degrees of chemical crosslinking maintained viscoelastic and sustained drug release for a long-term period of time at body temperature in vitro. With the addition of adipic dihydrazide (ADH) or 1-Ethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (EDCI), HA hydrosols transited from liquid to solid state at the gel point, with the G'/G″ ratio varying between 1.43 and 5.32 as a function of crosslinker concentration in the hydrogel phase. Ofloxacin (OFL) release from the mechanically mixed hydrosol system (CS-HA-A0-E0) and the micro-encapsulated hydrosol formulation (CS@HA-A0-E0) were respectively over 80% and 51% of the total drug load leaching out within 24 h. As for the drug-mixed hydrogel systems with low (CS-HA-A0.06-E0.15) and high (CS-HA-A0.06-E0.30) crosslinking density, the OFL release rate reached 38.5 and 46.6% respectively, while the micro-encapsulated hydrogel systems with low (CS@HA-A0.06-E0.15) and high (CS@HA-A0.6-E0.30) showed only (11.9 ± 2.7)% and (17.4 ± 3.5)% drug release respectively. A one-step in-situ drug-capsulizing method is developed to fabricate a resorbable hydrogel punctal plug with extended drug release. The chemistry of the crosslinking reaction involves the formation of highly biocompatible HA derivatives. Thus, the hydrogel can be used directly in the tear drainage canalicular system.

An interpenetrating HA/G/CS biomimic hydrogel via Diels-Alder click chemistry for cartilage tissue engineering.

PubMed

Yu, Feng; Cao, Xiaodong; Zeng, Lei; Zhang, Qing; Chen, Xiaofeng

2013-08-14

In order to mimic the natural cartilage extracellular matrix, a novel biological degradable interpenetrating network hydrogel was synthesized from the gelatin (G), hyaluronic acid (HA) and chondroitin sulfate (CS) by Diels-Alder "click" chemistry. HA was modified with furylamine and G was modified with furancarboxylic acid respectively. (1)H NMR spectra and elemental analysis showed that the substitution degrees of HA-furan and G-furan were 71.5% and 44.5%. Then the hydrogels were finally synthesized by cross-linking furan-modified HA and G derivatives with dimaleimide poly(ethylene glycol) (MAL-PEG-MAL). The mechanical and degradation properties of the hydrogels could be tuned simply through varying the molar ratio between furan and maleimide. Rheological, mechanical and degradation studies demonstrated that the Diels-Alder "click" chemistry is an efficient method for preparing high performance biological interpenetrating hydrogels. This biomimic hydrogel with improved mechanical properties could have great potential applications in cartilage tissue engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of three-dimensional hyaluronic acid microenvironments on mesenchymal stem cell chondrogenesis.

PubMed

Chung, Cindy; Burdick, Jason A

2009-02-01

Mesenchymal stem cells (MSCs) are multipotent progenitor cells whose plasticity and self-renewal capacity have generated significant interest for applications in tissue engineering. The objective of this study was to investigate MSC chondrogenesis in photo-cross-linked hyaluronic acid (HA) hydrogels. Because HA is a native component of cartilage, and MSCs may interact with HA via cell surface receptors, these hydrogels could influence stem cell differentiation. In vitro and in vivo cultures of MSC-laden HA hydrogels permitted chondrogenesis, measured by the early gene expression and production of cartilage-specific matrix proteins. For in vivo culture, MSCs were encapsulated with and without transforming growth factor beta-3 (TGF-beta3) or pre-cultured for 2 weeks in chondrogenic medium before implantation. Up-regulation of type II collagen, aggrecan, and sox 9 was observed for all groups over MSCs at the time of encapsulation, and the addition of TGF-beta3 further enhanced the expression of these genes. To assess the influence of scaffold chemistry on chondrogenesis, HA hydrogels were compared with relatively inert poly(ethylene glycol) (PEG) hydrogels and showed enhanced expression of cartilage-specific markers. Differences between HA and PEG hydrogels in vivo were most noticeable for MSCs and polymer alone, indicating that hydrogel chemistry influences the commitment of MSCs to undergo chondrogenesis (e.g., approximately 43-fold up-regulation of type II collagen of MSCs in HA over PEG hydrogels). Although this study investigated only early markers of tissue regeneration, these results emphasize the importance of material cues in MSC differentiation microenvironments, potentially through interactions between scaffold materials and cell surface receptors.

Preparation of hyaluronic acid micro-hydrogel by biotin-avidin-specific bonding for doxorubicin-targeted delivery.

PubMed

Cui, Yuan; Li, Yanhui; Duan, Qian; Kakuchi, Toyoji

2013-01-01

Hyaluronic acid is a naturally ionic polysaccharide with cancer cell selectivity. It is an ideal candidate material for delivery of anticancer agents. In this study, hyaluronic acid (HA) micro-hydrogel loaded with anticancer drugs was prepared by the biotin-avidin system approach. Firstly, carboxyl groups on HA were changed into amino groups with adipic acid dihydrazide (ADH) to graft with biotin by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride named as HA-biotin. When HA-biotin solution mixed with doxorubicin hydrochloride (DOX·HCl) was blended with neutravidin, the micro-hydrogels would be formed with DOX loading. If excess biotin was added into the microgel, it would be disjointed, and DOX will be released quickly. The results of the synthesis procedure were characterized by (1)H-NMR and FTIR; ADH and biotin have been demonstrated to graft on the HA molecule. A field emission scanning electron microscope was used to observe morphologies of HA micro-hydrogels. Furthermore, the in vitro DOX release results revealed that the release behaviors can be adjusted by adding biotin. Therefore, the HA micro-hydrogel can deliver anticancer drugs efficiently, and the rate of release can be controlled by biotin-specific bonding with the neutravidin. Consequently, the micro-hydrogel will perform the promising property of switching in the specific site in cancer therapy.

Research on torsional friction behavior and fluid load support of PVA/HA composite hydrogel.

PubMed

Chen, Kai; Zhang, Dekun; Yang, Xuehui; Cui, Xiaotong; Zhang, Xin; Wang, Qingliang

2016-09-01

Hydrogels have been extensively studied for use as synthetic articular cartilage. This study aimed to investigate (1) the torsional friction contact state and the transformation mechanism of PVA/HA composite hydrogel against CoCrMo femoral head and (2) effects of load and torsional angle on torsional friction behavior. The finite element method was used to study fluid load support of PVA/HA composite hydrogel. Results show fluid loss increases gradually of PVA/HA composite hydrogel with torsional friction time, leading to fluid load support decreases. The contact state changes from full slip state to stick-slip mixed state. As the load increases, friction coefficient and adhesion zone increase gradually. As the torsional angle increases, friction coefficient and slip trend of the contact interface increase, resulting in the increase of the slip zone and the reduction of the adhesion zone. Fluid loss increases of PVA/HA composite hydrogel as the load and the torsional angle increase, which causes the decrease of fluid load support and the increase of friction coefficient. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rheological performance of bacterial cellulose based nonmineralized and mineralized hydrogel scaffolds

NASA Astrophysics Data System (ADS)

Basu, Probal; Saha, Nabanita; Bandyopadhyay, Smarak; Saha, Petr

2017-05-01

Bacterial cellulose (BC) based hydrogels (BC-PVP and BC-CMC) are modified with β-tri-calcium phosphate (β-TCP) and hydroxyapatite (HA) to improve the structural and functional properties of the existing hydrogel scaffolds. The modified hydrogels are then biomineralized with CaCO3 following liquid diffusion technique, where salt solutions of Na2CO3 (5.25 g/100 mL) and CaCl2 (7.35 g/100 mL) were involved. The BC-PVP and BC-CMC are being compared with the non-mineralized (BC-PVP-β-TCP/HA and BC-CMC-β-TCP/HA) and biomineralized (BC-PVP-β-TCP/HA-CaCO3 and BC-CMC-β-TCP/HA-CaCO3) hydrogels on the basis of their structural and rheological properties. The Fourier Transform Infrared (FTIR) spectral analysis demonstrated the presence of BC, CMC, PVP, β-TCP, HA in the non-mineralized and BC, CMC, PVP, β-TCP, HA and CaCO3 in the biomineralized samples. Interestingly, the morphological property of non-mineralized and biomineralized, hydrogels are different than that of BC-PVP and BC-CMC based novel biomaterials. The Scanning Electron Microscopic (SEM) images of the before mentioned samples reveal the denser structures than BC-PVP and BC-CMC, which exhibits the changes in their pore sizes. Concerning rheological analysis point of view, all the non-mineralized and biomineralized hydrogel scaffolds have shown significant elastic property. Additionally, the complex viscosity (η*) values have also found in decreasing order with the increase of angular frequency (ω) 0.1 rad.sec-1 to 100 rad.sec-1. All these BC based hydrogel scaffolds are elastic in nature, can be recommended for their application as an implant for bone tissue engineering.

[PREPARATION AND BIOCOMPATIBILITY OF IN SITU CROSSLINKING HYALURONIC ACID HYDROGEL].

PubMed

Liang, Jiabi; Li, Jun; Wang, Ting; Liang, Yuhong; Zou, Xuenong; Zhou, Guangqian; Zhou, Zhiyu

2016-06-08

To fabricate in situ crosslinking hyaluronic acid hydrogel and evaluate its biocompatibility in vitro. The acrylic acid chloride and polyethylene glycol were added to prepare crosslinking agent polyethylene glycol acrylate (PEGDA), and the molecular structure of PEGDA was analyzed by Flourier transformation infrared spectroscopy and 1H nuclear magnetic resonance spectroscopy. Hyaluronic acid hydrogel was chemically modified to prepare hyaluronic acid thiolation (HA-SH). And the degree of HA-SH was analyzed qualitatively and quantitatively by Ellman method. HA-SH solution in concentrations ( W/V ) of 0.5%, 1.0%, and 1.5% and PEGDA solution in concentrations ( W/V ) of 2%, 4%, and 6% were prepared with PBS. The two solutions were mixed in different ratios, and in situ crosslinking hyaluronic acid hydrogel was obtained; the crosslinking time was recorded. The cellular toxicity of in situ crosslinking hyaluronic acid hydrogel (1.5% HA-SH and 4% PEGDA mixed) was tested by L929 cells. Meanwhile, the biocompatibility of hydrogel was tested by co-cultured with human bone mesenchymal stem cells (hBMSCs). Flourier transformation infrared spectroscopy showed that most hydroxyl groups were replaced by acrylate groups; 1H nuclear magnetic resonance spectroscopy showed 3 characteristic peaks of hydrogen representing acrylate and olefinic bond at 5-7 ppm. The thiolation yield of HA-SH was 65.4%. In situ crosslinking time of hyaluronic acid hydrogel was 2 to 70 minutes in the PEGDA concentrations of 2%-6% and HA-SH concentrations of 0.5%-1.5%. The hyaluronic acid hydrogel appeared to be transparent. The toxicity grade of leaching solution of hydrogel was grade 1. hBMSCs grew well and distributed evenly in hydrogel with a very high viability. In situ crosslinking hyaluronic acid hydrogel has low cytotoxicity, good biocompatibility, and controllable crosslinking time, so it could be used as a potential tissue engineered scaffold or repairing material for tissue regeneration.

Enzymatically crosslinked silk-hyaluronic acid hydrogels.

PubMed

Raia, Nicole R; Partlow, Benjamin P; McGill, Meghan; Kimmerling, Erica Palma; Ghezzi, Chiara E; Kaplan, David L

2017-07-01

In this study, silk fibroin and hyaluronic acid (HA) were enzymatically crosslinked to form biocompatible composite hydrogels with tunable mechanical properties similar to that of native tissues. The formation of di-tyrosine crosslinks between silk fibroin proteins via horseradish peroxidase has resulted in a highly elastic hydrogel but exhibits time-dependent stiffening related to silk self-assembly and crystallization. Utilizing the same method of crosslinking, tyramine-substituted HA forms hydrophilic and bioactive hydrogels that tend to have limited mechanics and degrade rapidly. To address the limitations of these singular component scaffolds, HA was covalently crosslinked with silk, forming a composite hydrogel that exhibited both mechanical integrity and hydrophilicity. The composite hydrogels were assessed using unconfined compression and infrared spectroscopy to reveal of the physical properties over time in relation to polymer concentration. In addition, the hydrogels were characterized by enzymatic degradation and for cytotoxicity. Results showed that increasing HA concentration, decreased gelation time, increased degradation rate, and reduced changes that were observed over time in mechanics, water retention, and crystallization. These hydrogel composites provide a biologically relevant system with controllable temporal stiffening and elasticity, thus offering enhanced tunable scaffolds for short or long term applications in tissue engineering. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-01-01

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

In situ synthesis of bilayered gradient poly(vinyl alcohol)/hydroxyapatite composite hydrogel by directional freezing-thawing and electrophoresis method.

PubMed

Su, Cui; Su, Yunlan; Li, Zhiyong; Haq, Muhammad Abdul; Zhou, Yong; Wang, Dujin

2017-08-01

Bilayered poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) composite hydrogels with anisotropic and gradient mechanical properties were prepared by the combination of directional freezing-thawing (DFT) and electrophoresis method. Firstly, PVA hydrogels with aligned channel structure were prepared by the DFT method. Then, HA nanoparticles were in situ synthesized within the PVA hydrogels via electrophoresis. By controlling the time of the electrophoresis process, a bilayered gradient hydrogel containing HA particles in only half of the gel region was obtained. The PVA/HA composite hydrogel exhibited gradient mechanical strength depending on the distance to the cathode. The gradient initial tensile modulus ranging from 0.18MPa to 0.27MPa and the gradient initial compressive modulus from 0.33MPa to 0.51MPa were achieved. The binding strength of the two regions was relatively high and no apparent internal stress or defect was observed at the boundary. The two regions of the bilayered hydrogel also showed different osteoblast cell adhesion properties. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2013-06-05

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

Stress relaxing hyaluronic acid-collagen hydrogels promote cell spreading, fiber remodeling, and focal adhesion formation in 3D cell culture.

PubMed

Lou, Junzhe; Stowers, Ryan; Nam, Sungmin; Xia, Yan; Chaudhuri, Ovijit

2018-02-01

The physical and architectural cues of the extracellular matrix (ECM) play a critical role in regulating important cellular functions such as spreading, migration, proliferation, and differentiation. Natural ECM is a complex viscoelastic scaffold composed of various distinct components that are often organized into a fibrillar microstructure. Hydrogels are frequently used as synthetic ECMs for 3D cell culture, but are typically elastic, due to covalent crosslinking, and non-fibrillar. Recent work has revealed the importance of stress relaxation in viscoelastic hydrogels in regulating biological processes such as spreading and differentiation, but these studies all utilize synthetic ECM hydrogels that are non-fibrillar. Key mechanotransduction events, such as focal adhesion formation, have only been observed in fibrillar networks in 3D culture to date. Here we present an interpenetrating network (IPN) hydrogel system based on HA crosslinked with dynamic covalent bonds and collagen I that captures the viscoelasticity and fibrillarity of ECM in tissues. The IPN hydrogels exhibit two distinct processes in stress relaxation, one from collagen and the other from HA crosslinking dynamics. Stress relaxation in the IPN hydrogels can be tuned by modulating HA crosslinker affinity, molecular weight of the HA, or HA concentration. Faster relaxation in the IPN hydrogels promotes cell spreading, fiber remodeling, and focal adhesion (FA) formation - behaviors often inhibited in other hydrogel-based materials in 3D culture. This study presents a new, broadly adaptable materials platform for mimicking key ECM features of viscoelasticity and fibrillarity in hydrogels for 3D cell culture and sheds light on how these mechanical and structural cues regulate cell behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Extended release of hyaluronic acid from hydrogel contact lenses for dry eye syndrome.

PubMed

Maulvi, Furqan A; Soni, Tejal G; Shah, Dinesh O

2015-01-01

Current dry eye treatment includes delivering comfort enhancing agents to the eye via eye drops, but low residence time of eye drops leads to low bioavailability. Frequent administration leads to incompliance in patients, so there is a great need for medical device such as contact lenses to treat dry eye. Studies in the past have demonstrated the efficacy of hyaluronic acid (HA) in the treatment of dry eyes using eye drops. In this paper, we present two methods to load HA in hydrogel contact lenses, soaking method and direct entrapment. The contact lenses were characterized by studying their optical and physical properties to determine their suitability as extended wear contact lenses. HA-laden hydrogel contact lenses prepared by soaking method showed release up to 48 h with acceptable physical and optical properties. Hydrogel contact lenses prepared by direct entrapment method showed significant sustained release in comparison to soaking method. HA entrapped in hydrogels resulted in reduction in % transmittance, sodium ion permeability and surface contact angle, while increase in % swelling. The impact on each of these properties was proportional to HA loading. The batch with 200-μg HA loading showed all acceptable values (parameters) for contact lens use. Results of cytotoxicity study indicated the safety of hydrogel contact lenses. In vivo pharmacokinetics studies in rabbit tear fluid showed dramatic increase in HA mean residence time and area under the curve with lenses in comparison to eye drop treatment. The study demonstrates the promising potential of delivering HA through contact lenses for the treatment of dry eye syndrome.

Rheological study of in-situ crosslinkable hydrogels based on hyaluronanic acid, collagen and sericin.

PubMed

Vulpe, Raluca; Le Cerf, Didier; Dulong, Virginie; Popa, Marcel; Peptu, Catalina; Verestiuc, Liliana; Picton, Luc

2016-12-01

The elaboration of chemically crosslinked hydrogels based on collagen (C), hyaluronanic acid (HA) and sericin (S) with different polymer ratios was investigated by in-situ rheology. This reaction was performed via amide or ester bond reaction activated by carbodiimide, in pure water. Prior to molecule crosslinking, the rheological behaviour of the biopolymers (alone or in mixture) was characterized in a semi-dilute concentration regime. Both flow and dynamic measurements showed that uncrosslinked collagen alone appears to be rather elastic with yield stress properties, whereas uncrosslinked HA alone appears to be rather shear thinning and viscoelastic in agreement with entangled polymer behaviour. Sericin exhibited Newtonian low viscosity behaviour according to its very low molar mass. Before crosslinking, HA exhibited viscoelastic behaviour at concentrations above the critical entangled concentration (C*) in the mixtures, thus HA shows promise as a matrix for future crosslinked networks, whereas sericin did not significantly modify the rheology. During the reaction, followed by rheology, the kinetics were slower for pure HA systems compared with the mixtures (i.e., with added collagen and/or to a lesser extent sericin). At the same time, the final network of hydrogels (i.e., the elastic modulus) was more structured in the mixture based systems. This result is explained by ester bonds (the only possibility for pure HA systems), which are less favourable and reactive than amide bonds (possible with sericin and collagen). The presence of collagen in the HA matrix reinforced the hydrogel network. SEM studies confirmed the structure of the hydrogels, and in vitro degradability was globally consistent with the effect of the selected enzyme according to the hydrogel composition. All the elaborated hydrogels were non-cytotoxic in vitro. Copyright © 2016 Elsevier B.V. All rights reserved.

Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.

PubMed

Korogiannaki, Myrto; Guidi, Giuliano; Jones, Lyndon; Sheardown, Heather

2015-09-01

This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile. © The Author(s) 2015.

A bioprintable form of chitosan hydrogel for bone tissue engineering.

PubMed

Demirtaş, Tuğrul Tolga; Irmak, Gülseren; Gümüşderelioğlu, Menemşe

2017-07-13

Bioprinting can be defined as 3D patterning of living cells and other biologics by filling and assembling them using a computer-aided layer-by-layer deposition approach to fabricate living tissue and organ analogs for tissue engineering. The presence of cells within the ink to use a 'bio-ink' presents the potential to print 3D structures that can be implanted or printed into damaged/diseased bone tissue to promote highly controlled cell-based regeneration and remineralization of bone. In this study, it was shown for the first time that chitosan solution and its composite with nanostructured bone-like hydroxyapatite (HA) can be mixed with cells and printed successfully. MC3T3-E1 pre-osteoblast cell laden chitosan and chitosan-HA hydrogels, which were printed with the use of an extruder-based bioprinter, were characterized by comparing these hydrogels to alginate and alginate-HA hydrogels. Rheological analysis showed that all groups had viscoelastic properties. It was also shown that under simulated physiological conditions, chitosan and chitosan-HA hydrogels were stable. Also, the viscosity values of the bio-solutions were in an applicable range to be used in 3D bio-printers. Cell viability and proliferation analyses documented that after printing with bio-solutions, cells continued to be viable in all groups. It was observed that cells printed within chitosan-HA composite hydrogel had peak expression levels for early and late stages osteogenic markers. It was concluded that cells within chitosan and chitosan-HA hydrogels had mineralized and differentiated osteogenically after 21 days of culture. It was also discovered that chitosan is superior to alginate, which is the most widely used solution preferred in bioprinting systems, in terms of cell proliferation and differentiation. Thus, applicability and printability of chitosan as a bio-printing solution were clearly demonstrated. Furthermore, it was proven that the presence of bone-like nanostructured HA in alginate and chitosan hydrogels improved cell viability, proliferation and osteogenic differentiation.

Gellan gum-hyaluronic acid spongy-like hydrogels and cells from adipose tissue synergize promoting neoskin vascularization.

PubMed

Cerqueira, Mariana Teixeira; da Silva, Lucília Pereira; Santos, Tírcia Carlos; Pirraco, Rogério Pedro; Correlo, Vítor Manuel; Reis, Rui Luís; Marques, Alexandra Pinto

2014-11-26

Currently available substitutes for skin wound healing often result in the formation of nonfunctional neotissue. Thus, urgent care is still needed to promote an effective and complete regeneration. To meet this need, we proposed the assembling of a construct that takes advantage of cell-adhesive gellan gum-hyaluronic acid (GG-HA) spongy-like hydrogels and a powerful cell-machinery obtained from adipose tissue, human adipose stem cells (hASCs), and microvascular endothelial cells (hAMECs). In addition to a cell-adhesive character, GG-HA spongy-like hydrogels overpass limitations of traditional hydrogels, such as reduced physical stability and limited manipulation, due to improved microstructural arrangement characterized by pore wall thickening and increased mean pore size. The proposed constructs combining cellular mediators of the healing process within the spongy-like hydrogels that intend to recapitulate skin matrix aim to promote neoskin vascularization. Stable and off-the-shelf dried GG-HA polymeric networks, rapidly rehydrated at the time of cell seeding then depicting features of both sponges and hydrogels, enabled the natural cell entrapment/encapsulation and attachment supported by cell-polymer interactions. Upon transplantation into mice full-thickness excisional wounds, GG-HA spongy-like hydrogels absorbed the early inflammatory cell infiltrate and led to the formation of a dense granulation tissue. Consequently, spongy-like hydrogel degradation was observed, and progressive wound closure, re-epithelialization, and matrix remodelling was improved in relation to the control condition. More importantly, GG-HA spongy-like hydrogels promoted a superior neovascularization, which was enhanced in the presence of human hAMECs, also found in the formed neovessels. These observations highlight the successful integration of a valuable matrix and prevascularization cues to target angiogenesis/neovascularization in skin full-thickness excisional wounds.

Compressive and swelling behavior of cuttlebone derived hydroxyapatite loaded PVA hydrogel implants for articular cartilage

NASA Astrophysics Data System (ADS)

Kumar, B. Y. Santosh; Kumar, G. C. Mohan; Isloor, Arun M.

2018-04-01

Developing a novel antibacterial, nontoxic and biocompatible hydrogel with superior physio mechanical properties is still becoming a challenge. Herein, we synthesize hydroxyapatite (HA) powder from cuttlefish bone and prepare a series of stiff, tough, high strength, biocompatible hydrogel reinforced with HA by integrating glutaraldehyde into PVA/HA. Powder was characterized by SEM and XRD. Compressive strength and swelling properties are studied and compare the results with the properties of healthy natural articular cartilage.

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

PubMed Central

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. PMID:24141109

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

NASA Astrophysics Data System (ADS)

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

2011-01-01

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

Zwitterionic Hydrogel-Biopolymer Assembly towards Biomimetic Superlubricants

NASA Astrophysics Data System (ADS)

Seekell, Raymond; Zhu, Elaine

2014-03-01

One superlubricant in nature is the synovial fluid (SF), comprising of a high molecular weight polysaccharide, hyaluronic acid (HA), and a globule protein, lubricin. In this bio-inspired materials research, we have explored hydrogel particles to mimic lubricin as a ``ball-bearing'' and control their interaction with the viscoelastic HA matrix. Biocompatible poly(N-[2-(Methacyloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide) (PMSA) hydrogel particles are synthesized to examine the electrostatic induced assembly of PMSA-HA supramolecular complexes in aqueous solutions. Fluorescence microscopy and rheology experiments have characterized the tunable network structure and viscoelastic properties of PMSA-HA aggregates by HA concentration and ionic conditions in aqueous solution. When being grafted to a solid surface, the PMSA-HA composite thin film exhibits superior low biofouling and friction performance, suggesting great promises as artificial superlubricants.

Hyaluronan (HA) interacting proteins RHAMM and hyaluronidase impact prostate cancer cell behavior and invadopodia formation in 3D HA-based hydrogels.

PubMed

Gurski, Lisa A; Xu, Xian; Labrada, Lyana N; Nguyen, Ngoc T; Xiao, Longxi; van Golen, Kenneth L; Jia, Xinqiao; Farach-Carson, Mary C

2012-01-01

To study the individual functions of hyaluronan interacting proteins in prostate cancer (PCa) motility through connective tissues, we developed a novel three-dimensional (3D) hyaluronic acid (HA) hydrogel assay that provides a flexible, quantifiable, and physiologically relevant alternative to current methods. Invasion in this system reflects the prevalence of HA in connective tissues and its role in the promotion of cancer cell motility and tissue invasion, making the system ideal to study invasion through bone marrow or other HA-rich connective tissues. The bio-compatible cross-linking process we used allows for direct encapsulation of cancer cells within the gel where they adopt a distinct, cluster-like morphology. Metastatic PCa cells in these hydrogels develop fingerlike structures, "invadopodia", consistent with their invasive properties. The number of invadopodia, as well as cluster size, shape, and convergence, can provide a quantifiable measure of invasive potential. Among candidate hyaluronan interacting proteins that could be responsible for the behavior we observed, we found that culture in the HA hydrogel triggers invasive PCa cells to differentially express and localize receptor for hyaluronan mediated motility (RHAMM)/CD168 which, in the absence of CD44, appears to contribute to PCa motility and invasion by interacting with the HA hydrogel components. PCa cell invasion through the HA hydrogel also was found to depend on the activity of hyaluronidases. Studies shown here reveal that while hyaluronidase activity is necessary for invadopodia and inter-connecting cluster formation, activity alone is not sufficient for acquisition of invasiveness to occur. We therefore suggest that development of invasive behavior in 3D HA-based systems requires development of additional cellular features, such as activation of motility associated pathways that regulate formation of invadopodia. Thus, we report development of a 3D system amenable to dissection of biological processes associated with cancer cell motility through HA-rich connective tissues.

3-Dimensional functionalized polycaprolactone-hyaluronic acid hydrogel constructs for bone tissue engineering.

PubMed

Hamlet, Stephen M; Vaquette, Cedryck; Shah, Amit; Hutmacher, Dietmar W; Ivanovski, Saso

2017-04-01

Alveolar bone regeneration remains a significant clinical challenge in periodontology and dental implantology. This study assessed the mineralized tissue forming potential of 3-D printed medical grade polycaprolactone (mPCL) constructs containing osteoblasts (OB) encapsulated in a hyaluronic acid (HA)-hydrogel incorporating bone morphogenetic protein-7 (BMP-7). HA-hydrogels containing human OB ± BMP-7 were prepared. Cell viability, osteogenic gene expression, mineralized tissue formation and BMP-7 release in vitro, were assessed by fluorescence staining, RT-PCR, histological/μ-CT examination and ELISA respectively. In an athymic rat model, subcutaneous ectopic mineralized tissue formation in mPCL-hydrogel constructs was assessed by μ-CT and histology. Osteoblast encapsulation in HA-hydrogels did not detrimentally effect cell viability, and 3-D culture in osteogenic media showed mineralized collagenous matrix formation after 6 weeks. BMP-7 release from the hydrogel was biphasic, sustained and increased osteogenic gene expression in vitro. After 4 weeks in vivo, mPCL-hydrogel constructs containing BMP-7 formed significantly more volume (mm 3 ) of vascularized bone-like tissue. Functionalized mPCL-HA hydrogel constructs provide a favourable environment for bone tissue engineering. Although encapsulated cells contributed to mineralized tissue formation within the hydrogel in vitro and in vivo, their addition did not result in an improved outcome compared to BMP-7 alone. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An injectable oxidated hyaluronic acid/adipic acid dihydrazide hydrogel as a vitreous substitute.

PubMed

Su, Wen-Yu; Chen, Ko-Hua; Chen, Yu-Chun; Lee, Yen-Hsien; Tseng, Ching-Li; Lin, Feng-Huei

2011-01-01

Vitrectomy is a common procedure for treating ocular-related diseases. The surgery involves removing the vitreous humor from the center of the eye, and vitreous substitutes are needed to replace the vitreous humor after vitrectomy. In the present study, we developed a colorless, transparent and injectable hydrogel with appropriate refractive index as a vitreous substitute. The hydrogel is formed by oxidated hyaluronic acid (oxi-HA) cross-linked with adipic acid dihydrazide (ADH). Hyaluronic acid (HA) was oxidized by sodium periodate to create aldehyde functional groups, which could be cross-linked by ADH. The refractive index of this hydrogel ranged between 1.3420 and 1.3442, which is quite similar to human vitreous humor (1.3345). The degradation tests demonstrated that the hydrogel could maintain the gel matrix over 35 days, depending on the ADH concentration. In addition, the cytotoxicity was evaluated on retina pigmented epithelium (RPE) cells cultivated following the ISO standard (tests for in vitro cytotoxicity), and the hydrogel was found to be non-toxic. In a preliminary animal study, the oxi-HA/ADH hydrogel was injected into the vitreous cavity of rabbit eyes. The evaluations of slit-lamp observation, intraocular pressure, cornea thickness and histological examination showed no significant abnormal biological reactions for 3 weeks. This study suggests that the injectable oxi-HA/ADH hydrogel should be a potential vitreous substitute. Koninklijke Brill NV, Leiden, 2011

Enzyme-mediated hyaluronic acid-tyramine hydrogels for the propagation of human embryonic stem cells in 3D.

PubMed

Xu, Keming; Narayanan, Karthikeyan; Lee, Fan; Bae, Ki Hyun; Gao, Shujun; Kurisawa, Motoichi

2015-09-01

The propagation of human embryonic stem cells (hESCs) in three-dimensional (3D) scaffolds facilitates the cell expansion process and supplies pluripotent cells of high quality for broad-spectrum applications in regenerative medicine. Herein, we report an enzyme-mediated hyaluronic acid-tyramine (HA-Tyr) hydrogel that encapsulated and propagated hESCs in 3D. HA-Tyr hydrogels were formed by crosslinking the tyramine moieties with horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). By changing the HRP and H2O2 concentration, we prepared HA-Tyr hydrogels of different mechanical strength and studied the self-renewal properties of hESCs in these scaffolds. We observed that both the chemical composition and mechanical strength of substrates were important factors affecting cell proliferation and pluripotency. The HA-Tyr hydrogel with a compressive modulus of ∼350Pa supported the proliferation of hESCs at the pluripotent state in both mTeSR1 medium and mouse embryonic fibroblast (MEF)-conditioned medium. Immunohistochemical analyses revealed that hESCs proliferated well and formed spheroid structures in 3D, without undergoing apoptosis. The hESCs cultured in HA-Tyr hydrogels showed high expression of CD44 and pluripotency markers. These cells exhibited the capability to form cell derivatives of all three embryonic germ layers in vitro and in vivo. In addition, the genetic integrity of the hESCs was unaffected in the 3D cultivation system. The scope of this study is to provide a stable 3D cultivation system for the expansion of human embryonic stem cells (hESCs) towards clinical applications. We report an enzyme mediated hyaluronic acid-tyramine (HA-Tyr) hydrogel that encapsulated and propagated hESCs in 3D. Unlike other HA-based photo-crosslinked hydrogel systems reported, we investigated the effects of mechanical strength of hydrogels on the self-renewal properties of hESCs in 3D. Then, we characterized hESCs cultured in hydrogels with lower mechanical strength that best supported the self-renewal of hESCs. Hence, we demonstrated a reliable approach for the controlled propagation of hESCs in 3D. We believe that such an approach would facilitate the development of stem cell-based therapy towards clinical applications. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Implantation of hyaluronic acid hydrogel prevents the pain phenotype in a rat model of intervertebral disc injury

PubMed Central

Sakai, Daisuke; Dockery, Peter

2018-01-01

Painful intervertebral disc degeneration is mediated by inflammation that modulates glycosylation and induces hyperinnervation and sensory sensitization, which result in discogenic pain. Hyaluronic acid (HA) used as a therapeutic biomaterial can reduce inflammation and pain, but the effects of HA therapy on glycosylation and pain associated with disc degeneration have not been previously determined. We describe a novel rat model of pain induced by intervertebral disc injury, with validation of the pain phenotype by morphine treatment. Using this model, we assessed the efficacy of HA hydrogel for the alleviation of pain, demonstrating that it reduced nociceptive behavior, an effect associated with down-regulation of nociception markers and inhibition of hyperinnervation. Furthermore, HA hydrogel altered glycosylation and modulated key inflammatory and regulatory signaling pathways, resulting in attenuation of inflammation and regulation of matrix components. Our results suggest that HA hydrogel is a promising clinical candidate for the treatment of back pain caused by degenerated discs. PMID:29632893

The effect of hypoxia on thermosensitive poly(N-vinylcaprolactam) hydrogels with tunable mechanical integrity for cartilage tissue engineering.

PubMed

Lynch, Brandon; Crawford, Kristopher; Baruti, Omari; Abdulahad, Asem; Webster, Martial; Puetzer, Jennifer; Ryu, Chang; Bonassar, Lawrence J; Mendenhall, Juana

2017-10-01

Cartilage repair presents a daunting challenge in tissue engineering applications due to the low oxygen conditions (hypoxia) affiliated in diseased states. Hence, the use of biomaterial scaffolds with unique variability is imperative to treat diseased or damaged cartilage. Thermosensitive hydrogels show promise as injectable materials that can be used as tissue scaffolds for cartilage tissue regeneration. However, uses in clinical applications are limited to due mechanical stability and therapeutic efficacy to treat diseased tissue. In this study, several composite hydrogels containing poly(N-vinylcaprolactam) (PVCL) and methacrylated hyaluronic acid (meHA) were prepared using free radical polymerization to produce PVCL-graft-HA (PVCL-g-HA) and characterized using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and scanning electron microscopy. Lower critical solution temperatures and gelation temperatures were confirmed in the range of 33-34°C and 41-45°C, respectively. Using dynamic sheer rheology, the temperature dependence of elastic (G') and viscous (G″) modulus between 25°C and 45°C, revealed that PVCL-g-HA hydrogels at 5% (w/v) concentration exhibited the moduli of 7 Pa (G') to 4 Pa (G″). After 10 days at 1% oxygen, collagen production on PVCL-g-HA hydrogels was 153 ± 25 μg/mg (20%) and 106 ± 18 μg/mg showing a 10-fold increase compared to meHA controls. These studies show promise in PVCL-g-HA hydrogels for the treatment of diseased or damaged articular cartilage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1863-1873, 2017. © 2016 Wiley Periodicals, Inc.

Targeted Drug Delivery in the Suprachoroidal Space by Swollen Hydrogel Pushing.

PubMed

Jung, Jae Hwan; Desit, Patcharin; Prausnitz, Mark R

2018-04-01

The purpose is to target model drug particles to the posterior region of the suprachoroidal space (SCS) of the eye controlled via pushing by hydrogel swelling. A particle formulation containing 1% hyaluronic acid (HA) with fluorescent polymer particles and a hydrogel formulation containing 4% HA were introduced in a single syringe as two layers without mixing, and injected sequentially into the SCS of the rabbit eye ex vivo and in vivo using a microneedle. Distribution of particles in the eye was determined by microscopy. During injection, the particle formulation was pushed toward the middle of the SCS by the viscous hydrogel formulation, but less than 12% of particles reached the posterior SCS. After injection, the particle formulation was pushed further toward the macula and optic nerve in the posterior SCS by hydrogel swelling and spreading. Heating the eye to 37°C, or injecting in vivo decreased viscosity and mechanical strength of the hydrogel, thereby allowing it to swell and flow further in the SCS. A high salt concentration (9% NaCl) in the hydrogel formulation further increased hydrogel swelling due to osmotic flow into the hydrogel. In this way, up to 76% of particles were delivered to the posterior SCS from an injection made near the limbus. This study shows that model drug particles can be targeted to the posterior SCS by HA hydrogel swelling and pushing without particle functionalization or administering external driving forces.

Cold Spray Coating of Submicronic Ceramic Particles on Poly(vinyl alcohol) in Dry and Hydrogel States

NASA Astrophysics Data System (ADS)

Moreau, David; Borit, François; Corté, Laurent; Guipont, Vincent

2017-06-01

We report an approach using cold spray technology to coat poly(vinyl alcohol) (PVA) in polymer and hydrogel states with hydroxyapatite (HA). Using porous aggregated HA powder, we hypothesized that fragmentation of the powder upon cold spray could lead to formation of a ceramic coating on the surface of the PVA substrate. However, direct spraying of this powder led to complete destruction of the swollen PVA hydrogel substrate. As an alternative, HA coatings were successfully produced by spraying onto dry PVA substrates prior to swelling in water. Dense homogeneous HA coatings composed of submicron particles were obtained using rather low-energy spraying parameters (temperature 200-250 °C, pressure 1-3 MPa). Coated PVA substrates could swell in water without removal of the ceramic layer to form HA-coated hydrogels. Microscopic observations and in situ measurements were used to explain how local heating and impact of sprayed aggregates induced surface roughening and strong binding of HA particles to the molten PVA substrate. Such an approach could lead to design of ceramic coatings whose roughness and crystallinity can be finely adjusted to improve interfacing with biological tissues.

Dynamic compressive loading enhances cartilage matrix synthesis and distribution and suppresses hypertrophy in hMSC-laden hyaluronic acid hydrogels.

PubMed

Bian, Liming; Zhai, David Y; Zhang, Emily C; Mauck, Robert L; Burdick, Jason A

2012-04-01

Mesenchymal stem cells (MSCs) are being recognized as a viable cell source for cartilage repair, and there is growing evidence that mechanical signals play a critical role in the regulation of stem cell chondrogenesis and in cartilage development. In this study we investigated the effect of dynamic compressive loading on chondrogenesis, the production and distribution of cartilage specific matrix, and the hypertrophic differentiation of human MSCs encapsulated in hyaluronic acid (HA) hydrogels during long term culture. After 70 days of culture, dynamic compressive loading increased the mechanical properties, as well as the glycosaminoglycan (GAG) and collagen contents of HA hydrogel constructs in a seeding density dependent manner. The impact of loading on HA hydrogel construct properties was delayed when applied to lower density (20 million MSCs/ml) compared to higher seeding density (60 million MSCs/ml) constructs. Furthermore, loading promoted a more uniform spatial distribution of cartilage matrix in HA hydrogels with both seeding densities, leading to significantly improved mechanical properties as compared to free swelling constructs. Using a previously developed in vitro hypertrophy model, dynamic compressive loading was also shown to significantly reduce the expression of hypertrophic markers by human MSCs and to suppress the degree of calcification in MSC-seeded HA hydrogels. Findings from this study highlight the importance of mechanical loading in stem cell based therapy for cartilage repair in improving neocartilage properties and in potentially maintaining the cartilage phenotype.

Targeted Drug Delivery in the Suprachoroidal Space by Swollen Hydrogel Pushing

PubMed Central

Jung, Jae Hwan; Desit, Patcharin; Prausnitz, Mark R.

2018-01-01

Purpose The purpose is to target model drug particles to the posterior region of the suprachoroidal space (SCS) of the eye controlled via pushing by hydrogel swelling. Methods A particle formulation containing 1% hyaluronic acid (HA) with fluorescent polymer particles and a hydrogel formulation containing 4% HA were introduced in a single syringe as two layers without mixing, and injected sequentially into the SCS of the rabbit eye ex vivo and in vivo using a microneedle. Distribution of particles in the eye was determined by microscopy. Results During injection, the particle formulation was pushed toward the middle of the SCS by the viscous hydrogel formulation, but less than 12% of particles reached the posterior SCS. After injection, the particle formulation was pushed further toward the macula and optic nerve in the posterior SCS by hydrogel swelling and spreading. Heating the eye to 37°C, or injecting in vivo decreased viscosity and mechanical strength of the hydrogel, thereby allowing it to swell and flow further in the SCS. A high salt concentration (9% NaCl) in the hydrogel formulation further increased hydrogel swelling due to osmotic flow into the hydrogel. In this way, up to 76% of particles were delivered to the posterior SCS from an injection made near the limbus. Conclusions This study shows that model drug particles can be targeted to the posterior SCS by HA hydrogel swelling and pushing without particle functionalization or administering external driving forces. PMID:29677369

High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury

NASA Astrophysics Data System (ADS)

Khaing, Zin Z.; Milman, Brian D.; Vanscoy, Jennifer E.; Seidlits, Stephanie K.; Grill, Raymond J.; Schmidt, Christine E.

2011-08-01

A major hurdle for regeneration after spinal cord injury (SCI) is the ability of axons to penetrate and grow through the scar tissue. After SCI, inflammatory cells, astrocytes and meningeal cells all play a role in developing the glial scar. In addition, degradation of native high molecular weight (MW) hyaluronic acid (HA), a component of the extracellular matrix, has been shown to induce activation and proliferation of astrocytes. However, it is not known if the degradation of native HA actually enhances glial scar formation. We hypothesize that the presence of high MW HA (HA with limited degradation) after SCI will decrease glial scarring. Here, we demonstrate that high MW HA decreases cell proliferation and reduces chondroitin sulfate proteoglycan (CSPG) production in cultured neonatal and adult astrocytes. In addition, stiffness-matched high MW HA hydrogels crosslinked to resist degradation were implanted in a rat model of spinal dorsal hemisection injury. The numbers of immune cells (macrophages and microglia) detected at the lesion site in animals with HA hydrogel implants were significantly reduced at acute time points (one, three and ten days post-injury). Lesioned animals with HA implants also exhibited significantly lower CSPG expression at ten days post-injury. At nine weeks post-injury, animals with HA hydrogel implants exhibited a significantly decreased astrocytic response, but did not have significantly altered CSPG expression. Combined, these data suggest that high MW HA, when stabilized against degradation, mitigates astrocyte activation in vitro and in vivo. The presence of HA implants was also associated with a significant decrease in CSPG deposition at ten days after SCI. Therefore, HA-based hydrogel systems hold great potential for minimizing undesired scarring as part of future repair strategies after SCI.

High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury.

PubMed

Khaing, Zin Z; Milman, Brian D; Vanscoy, Jennifer E; Seidlits, Stephanie K; Grill, Raymond J; Schmidt, Christine E

2011-08-01

A major hurdle for regeneration after spinal cord injury (SCI) is the ability of axons to penetrate and grow through the scar tissue. After SCI, inflammatory cells, astrocytes and meningeal cells all play a role in developing the glial scar. In addition, degradation of native high molecular weight (MW) hyaluronic acid (HA), a component of the extracellular matrix, has been shown to induce activation and proliferation of astrocytes. However, it is not known if the degradation of native HA actually enhances glial scar formation. We hypothesize that the presence of high MW HA (HA with limited degradation) after SCI will decrease glial scarring. Here, we demonstrate that high MW HA decreases cell proliferation and reduces chondroitin sulfate proteoglycan (CSPG) production in cultured neonatal and adult astrocytes. In addition, stiffness-matched high MW HA hydrogels crosslinked to resist degradation were implanted in a rat model of spinal dorsal hemisection injury. The numbers of immune cells (macrophages and microglia) detected at the lesion site in animals with HA hydrogel implants were significantly reduced at acute time points (one, three and ten days post-injury). Lesioned animals with HA implants also exhibited significantly lower CSPG expression at ten days post-injury. At nine weeks post-injury, animals with HA hydrogel implants exhibited a significantly decreased astrocytic response, but did not have significantly altered CSPG expression. Combined, these data suggest that high MW HA, when stabilized against degradation, mitigates astrocyte activation in vitro and in vivo. The presence of HA implants was also associated with a significant decrease in CSPG deposition at ten days after SCI. Therefore, HA-based hydrogel systems hold great potential for minimizing undesired scarring as part of future repair strategies after SCI.

Probing vocal fold fibroblast response to hyaluronan in 3D contexts.

PubMed

Munoz-Pinto, Dany J; Jimenez-Vergara, Andrea Carolina; Gelves, L Marcela; McMahon, Rebecca E; Guiza-Arguello, Viviana; Hahn, Mariah S

2009-11-01

A number of treatments are being investigated for vocal fold (VF) scar, including designer implants. The aim of the present study was to validate a 3D model system for probing the effects of various bioactive moieties on VF fibroblast (VFF) behavior toward rational implant design. We selected poly(ethylene glycol) diacrylate (PEGDA) hydrogels as our base-scaffold due to their broadly tunable material properties. However, since cells encapsulated in PEGDA hydrogels are generally forced to take on rounded/stellate morphologies, validation of PEGDA gels as a 3D VFF model system required that the present work directly parallel previous studies involving more permissive scaffolds. We therefore chose to focus on hyaluronan (HA), a polysaccharide that has been a particular focus of the VF community. Toward this end, porcine VFFs were encapsulated in PEGDA hydrogels containing consistent levels of high Mw HA (HA(HMW)), intermediate Mw HA (HA(IMW)), or the control polysaccharide, alginate, and cultured for 7 and 21 days. HA(HMW) promoted sustained increases in active ERK1/2 relative to HA(IMW). Furthermore, VFFs in HA(IMW) gels displayed a more myofibroblast-like phenotype, higher elastin production, and greater protein kinase C (PkC) levels at day 21 than VFFs in HA(HMW) and alginate gels. The present results are in agreement with a previous 3D study of VFF responses to HA(IMW) relative to alginate in collagen-based scaffolds permissive of cell elongation, indicating that PEGDA hydrogels may serve as an effective 3D model system for probing at least certain aspects of VFF behavior. Copyright 2009 Wiley Periodicals, Inc.

Hyaluronic acid based hydrogel system for soft tissue regeneration and drug delivery

NASA Astrophysics Data System (ADS)

Jha, Amit Kumar

We have developed hyaluronic acid (HA)-based, biomimetic hydrogel matrices that are hierarchically structured, mechanically robust and biologically active. Specifically, HA-based hydrogel particles (HGPs) with controlled sizes, defined porosity, and improved stability were synthesized using different inverse emulsion systems and crosslinking chemistries. The resultant particles either contained residual functional groups or were rendered reactive by subsequent chemical modifications. HA-based doubly crosslinked networks (DXNs) were synthesized via covalent crosslinking of HA HGPs with soluble HA macromers carrying mutually reactive functional groups. These hybrid matrices are hierarchical in nature, consisting of densely crosslinked HGPs integrated in a loosely connected secondary matrix. Their mechanical properties and degradation kinetics can be readily tuned by varying the particle size, functional group density, intra- and interparticle crosslinking. To improve the biological functions of HA HGPs, perlecan domain I (PlnDI), a basement membrane proteoglycan that has strong affinity for various heparin binding growth factors (HBGFs), was successfully conjugated to the particles through the core protein via a flexible poly(ethylene glycol) (PEG) linker. The immobilized PlnDI maintains its ability to bind bone morphogenetic proteins (BMP-2) and modulates its in vitro release. A similar, sustained release of BMP-2 was achieved by encapsulating BMP-2-loaded HGPs within a photocrosslinked HA matrix. When encapsulated in HA DXNs, primary bovine chondrocytes were able to maintain their phenotype, proliferate readily and produce abundant glycosaminoglycan. Finally, cell-adhesive HA DXNs were fabricated by encapsulating gelatin-decorated HA HGPs in a secondary HA matrix. Human MSCs were shown to adhere to the composite matrix through the focal adhesion sites clustered on particle surface. The cell-adhesive composite matrices supported hMSC proliferation and migration into the gels. Human MSCs were undifferentiated during the early time points of culture, however differentiated into osteoblast phenotype after 28 days of culture. In summary, the HA-based hydrogel matrices are hierarchically structured, mechanically robust and enzymatically stable, capable of mediating cellular functions through the spatial and temporal presentation of defined biological cues. These hydrogel systems are promising candidates for soft tissue regeneration.

Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration.

PubMed

Radhakrishnan, Janani; Manigandan, Amrutha; Chinnaswamy, Prabu; Subramanian, Anuradha; Sethuraman, Swaminathan

2018-04-01

Fabrication of anisotropic osteochondral-mimetic scaffold with mineralized subchondral zone and gradient interface remains challenging. We have developed an injectable semi-interpenetrating network hydrogel construct with chondroitin sulfate nanoparticles (ChS-NPs) and nanohydroxyapatite (nHA) (∼30-90 nm) in chondral and subchondral hydrogel zones respectively. Mineralized subchondral hydrogel exhibited significantly higher osteoblast proliferation and alkaline phosphatase activity (p < 0.05). Osteochondral hydrogel exhibited interconnected porous structure and spatial variation with gradient interface of nHA and ChS-NPs. Microcomputed tomography (μCT) demonstrated nHA gradation while rheology showed predominant elastic modulus (∼930 Pa) at the interface. Co-culture of osteoblasts and chondrocytes in gradient hydrogels showed layer-specific retention of cells and cell-cell interaction at the interface. In vivo osteochondral regeneration by biphasic (nHA or ChS) and gradient (nHA + ChS) hydrogels was compared with control using rabbit osteochondral defect after 3 and 8 weeks. Complete closure of defect was observed in gradient (8 weeks) while defect remained in other groups. Histology demonstrated collagen and glycosaminoglycan deposition in neo-matrix and presence of hyaline cartilage-characteristic matrix, chondrocytes and osteoblasts. μCT showed mineralized neo-tissue formation, which was confined within the defect with higher bone mineral density in gradient (chondral: 0.42 ± 0.07 g/cc, osteal: 0.64 ± 0.08 g/cc) group. Further, biomechanical push-out studies showed significantly higher load for gradient group (378 ± 56 N) compared to others. Thus, the developed nano-engineered gradient hydrogel enhanced hyaline cartilage regeneration with subchondral bone formation and lateral host-tissue integration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anti-Fas conjugated hyaluronic acid microsphere gels for neural stem cell delivery.

PubMed

Shendi, Dalia; Albrecht, Dirk R; Jain, Anjana

2017-02-01

Central nervous system (CNS) injuries and diseases result in neuronal damage and loss of function. Transplantation of neural stem cells (NSCs) has been shown to improve locomotor function after transplantation. However, due to the immune and inflammatory response at the injury site, the survival rate of the engrafted cells is low. Engrafted cell viability has been shown to increase when transplanted within a hydrogel. Hyaluronic acid (HA) hydrogels have natural anti-inflammatory properties and the backbone can be modified to introduce bioactive agents, such as anti-Fas, which we have previously shown to promote NSC survival while suppressing immune cell activity in bulk hydrogels in vitro. Although bulk HA hydrogels have shown to promote stem cell survival, microsphere gels for NSC encapsulation and delivery may have additional advantages. In this study, a flow-focusing microfluidic device was used to fabricate either vinyl sulfone-modified HA (VS-HA) or anti-Fas-conjugated HA (anti-Fas HA) microsphere gels encapsulated with NSCs. The majority of encapsulated NSCs remained viable for at least 24 h in the VS-HA and anti-Fas HA microsphere gels. Moreover, T-cells cultured in suspension with the anti-Fas HA microsphere gels had reduced viability after contact with the microsphere gels compared to the media control and soluble anti-Fas conditions. This approach can be adapted to encapsulate various cell types for therapeutic strategies in other physiological systems in order to increase survival by reducing the immune response. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 608-618, 2017. © 2016 Wiley Periodicals, Inc.

Release of Ciprofloxacin-HCl and Dexamethasone Phosphate by Hyaluronic Acid Containing Silicone Polymers.

PubMed

Nguyen, Darrene; Hui, Alex; Weeks, Andrea; Heynen, Miriam; Joyce, Elizabeth; Sheardown, Heather; Jones, Lyndon

2012-04-19

The purpose of this study was to determine the effect of the covalent incorporation of hyaluronic acid (HA) into conventional hydrogel and hydrogels containing silicone as models for contact lens materials on the uptake and release of the fluoroquinolone antibiotic ciprofloxacin and the anti-inflammatory steroid dexamethasone phosphate. A 3 mg/mL ciprofloxacin solution (0.3% w/v) and a 1 mg/mL dexamethasone phosphate solution (0.1%) was prepared in borate buffered saline. Three hydrogel material samples (pHEMA; pHEMA TRIS; DMAA TRIS) were prepared with and without the covalent incorporation of HA of molecular weight (MW) 35 or 132 kDa. Hydrogel discs were punched from a sheet of material with a uniform diameter of 5 mm. Uptake kinetics were evaluated at room temperature by soaking the discs for 24 h. Release kinetics were evaluated by placing the drug-loaded discs in saline at 34 °C in a shaking water bath. At various time points over 6-7 days, aliquots of the release medium were assayed for drug amounts. The majority of the materials tested released sufficient drug to be clinically relevant in an ophthalmic application, reaching desired concentrations for antibiotic or anti-inflammatory activity in solution. Overall, the silicone-based hydrogels (pHEMA TRIS and DMAA TRIS), released lower amounts of drug than the conventional pHEMA material (p < 0.001). Materials with HA MW132 released more ciprofloxacin compared to materials with HA MW35 and lenses without HA (p < 0.02). Some HA-based materials were still releasing the drug after 6 days.

Antibody loaded collapsible hyaluronic acid hydrogels for intraocular delivery.

PubMed

Egbu, Raphael; Brocchini, Steve; Khaw, Peng T; Awwad, Sahar

2018-03-01

Injectable gels have the potential to encapsulate drugs for sustained release of protein therapeutics for use in the eye. Hyaluronic acid (HA) is a biodegradable clinically used material and poly N-isopropylacrylamide (pNIPAAM) is a stimuli responsive polymer that can display a lower critical solution temperature (LCST) at physiological conditions. Two gel systems incorporating HA were prepared in the presence of the antibody infliximab (INF): i) 1% and 5% tyramine-substituted HA (HA-Tyr) was enzymatically crosslinked in the presence of INF to form HA-Tyr-INF and ii) NIPAAM was chemically crosslinked in the presence of HA and INF with 1 and 3% poly(ethylene glycol) diacrylate (PEGDA) to form PEGDA-pNIPAAM-HA-INF. The PEGDA-pNIPAAM-HA-INF hydrogels displayed LCSTs at temperatures ranging from 31.4 ± 0.2 to 35.7 ± 0.3 °C. Although all the gels prepared were injectable, INF-loaded gels with lower crosslinking density (1% PEGDA-pNIPAAM-HA and 1% HA-Tyr) showed lower elastic (G') and viscous (G″) moduli compared to higher crosslinked gels (3% PEGDA-pNIPAAM-HA-INF and 5% HA-Tyr-INF) resulting in differences in swelling ratio (SR). Moduli may be correlated with overall stiffness of the gel. All hydrogels demonstrated sustained release of INF in a two-compartment in vitro outflow model of the human eye called the PK-Eye. The 1% PEGDA-pNIPAAM-HA-INF hydrogel displayed the slowest release (24.9 ± 0.4% INF release by day 9) in phosphate buffered saline (PBS, pH 7.4), which is a better release profile than the free drug alone (tested under the same conditions). These results suggest that PEGDA-pNIPAAM-HA has potential for the continued development of formulations to prolong the intraocular release of proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Engineering the bone-ligament interface using polyethylene glycol diacrylate incorporated with hydroxyapatite.

PubMed

Paxton, Jennifer Z; Donnelly, Kenneth; Keatch, Robert P; Baar, Keith

2009-06-01

Ligaments and tendons have previously been tissue engineered. However, without the bone attachment, implantation of a tissue-engineered ligament would require it to be sutured to the remnant of the injured native tissue. Due to slow repair and remodeling, this would result in a chronically weak tissue that may never return to preinjury function. In contrast, orthopaedic autograft reconstruction of the ligament often uses a bone-to-bone technique for optimal repair. Since bone-to-bone repairs heal better than other methods, implantation of an artificial ligament should also occur from bone-to-bone. The aim of this study was to investigate the use of a poly(ethylene glycol) diacrylate (PEGDA) hydrogel incorporated with hydroxyapatite (HA) and the cell-adhesion peptide RGD (Arg-Gly-Asp) as a material for creating an in vitro tissue interface to engineer intact ligaments (i.e., bone-ligament-bone). Incorporation of HA into PEG hydrogels reduced the swelling ratio but increased mechanical strength and stiffness of the hydrogels. Further, HA addition increased the capacity for cell growth and interface formation. RGD incorporation increased the swelling ratio but decreased mechanical strength and stiffness of the material. Optimum levels of cell attachment were met using a combination of both HA and RGD, but this material had no better mechanical properties than PEG alone. Although adherence of the hydrogels containing HA was achieved, failure occurs at about 4 days with 5% HA. Increasing the proportion of HA improved interface formation; however, with high levels of HA, the PEG HA composite became brittle. This data suggests that HA, by itself or with other materials, might be well suited for engineering the ligament-bone interface.

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

Development of a novel alginate-polyvinyl alcohol-hydroxyapatite hydrogel for 3D bioprinting bone tissue engineered scaffolds.

PubMed

Bendtsen, Stephanie T; Quinnell, Sean P; Wei, Mei

2017-05-01

Three-dimensional printed biomaterials used as personalized tissue substitutes have the ability to promote and enhance regeneration in areas of defected tissue. The challenge with 3D printing for bone tissue engineering remains the selection of a material with optimal rheological properties for printing in addition to biocompatibility and capacity for uniform cell incorporation. Hydrogel biomaterials may provide sufficient printability to allow cell encapsulation and bioprinting of scaffolds with uniform cell distribution. In this study, a novel alginate-polyvinyl alcohol (PVA)-hydroxyapatite (HA) hydrogel formulation with optimal rheological properties for 3D bioprinting of mouse calvaria 3T3-E1 (MC3T3) cells into scaffolds of high shape fidelity has been developed. A systematic investigation was conducted to determine the effect of varying concentrations of alginate, phosphate, calcium, and the PVA-HA suspension in the formulation on the resulting viscosity and thus printability of the hydrogel. HA, the main mineral component in natural bone, was incorporated into the hydrogel formulation to create a favorable bone-forming environment due to its excellent osteoconductivity. Degradation studies in α-MEM cell culture media showed that the 3D printed alginate-PVA-HA scaffolds remained in-tact for 14 days. MC3T3 cells were well distributed and encapsulated throughout the optimal hydrogel formulation and expressed high viability through the completion of the 3D printing process. Thus, the development of this novel, osteoconductive, biodegradable, alginate-PVA-HA formulation and its ability to 3D bioprint tissue engineered scaffolds make it a promising candidate for treating personalized bone defects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1457-1468, 2017. © 2017 Wiley Periodicals, Inc.

Investigation of Overrun-Processed Porous Hyaluronic Acid Carriers in Corneal Endothelial Tissue Engineering

PubMed Central

Lai, Jui-Yang; Cheng, Hsiao-Yun; Ma, David Hui-Kang

2015-01-01

Hyaluronic acid (HA) is a linear polysaccharide naturally found in the eye and therefore is one of the most promising biomaterials for corneal endothelial regenerative medicine. This study reports, for the first time, the development of overrun-processed porous HA hydrogels for corneal endothelial cell (CEC) sheet transplantation and tissue engineering applications. The hydrogel carriers were characterized to examine their structures and functions. Evaluations of carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted simultaneously for comparison. The results indicated that during the fabrication of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous biopolymer solutions can be used to enlarge pore structure and prevent dense surface skin formation. Among all the groups studied, the overrun-processed porous HA carriers show the greatest biological stability, the highest freezable water content and glucose permeability, and the minimized adverse effects on ionic pump function of rabbit CECs. After transfer and attachment of bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit model with corneal endothelial dysfunction. Clinical observations including slit-lamp biomicroscopy, specular microscopy, and corneal thickness measurements showed that the construct implants can regenerate corneal endothelium and restore corneal transparency at 4 weeks postoperatively. Our findings suggest that cell sheet transplantation using overrun-processed porous HA hydrogels offers a new way to reconstruct the posterior corneal surface and improve endothelial tissue function. PMID:26296087

Physicochemical properties of pH-sensitive hydrogels based on hydroxyethyl cellulose-hyaluronic acid and for applications as transdermal delivery systems for skin lesions.

PubMed

Kwon, Soon Sik; Kong, Bong Ju; Park, Soo Nam

2015-05-01

We investigated the physicochemical properties of pH-sensitive hydroxyethyl cellulose (HEC)/hyaluronic acid (HA) complex hydrogels containing isoliquiritigenin (ILTG), and discussed potential applications as transdermal delivery systems for the treatment of skin lesions caused by pH imbalance. HA has skin compatibility and pH functional groups and HEC serves as scaffold to build hydrogels with varied HCE:HA mass ratio. Hydrogels were synthesized via chemical cross-linking, and three-dimensional network structures were characterized via scanning electron microscopy (SEM). The swelling properties and polymer ratios of the hydrogels were investigated at pH values in the range 1-13. HECHA13 (i.e., an HEC:HA mass ratio of 1:3) was found to have optimal rheological and adhesive properties, and was used to investigate the drug release efficiency as a function of pH; the efficiency was greater than 70% at pH 7. Antimicrobial activity assays against Propionibacterium acnes were conducted to take advantage of the pH-sensitive properties of HECHA13. At pH 7, we found that HECHA13, which contained ILTG, inhibited the growth of P. acnes. Furthermore, HECHA13 was found to exhibit excellent permeability into the skin, which penetrated mostly via the hair follicle. These results indicate that this pH-sensitive hydrogel is effective as a transdermal delivery system for antimicrobial therapeutics, with potential applications in the treatment of acne. Copyright © 2015 Elsevier B.V. All rights reserved.

Hyaluronic acid-based scaffolds for tissue engineering.

PubMed

Chircov, Cristina; Grumezescu, Alexandru Mihai; Bejenaru, Ludovic Everard

2018-01-01

Hyaluronic acid (HA) is a natural glycosaminoglycan found in the extracellular matrix of most connective tissues. Due to its chemical structure, HA is a hydrophilic polymer and it is characterized by a fast degradation rate. HA-based scaffolds for tissue engineering are intensively studied due to their increased biocompatibility, biodegradability and chemical modification. Depending on the processing technique, scaffolds can be prepared in the form of hydrogels, sponges, cryogels, and injectable hydrogels, all discussed in this review.

Influence of Pre-Freezing Temperature on the Corneal Endothelial Cytocompatibility and Cell Delivery Performance of Porous Hyaluronic Acid Hydrogel Carriers.

PubMed

Lai, Jui-Yang

2015-08-11

The development of porous hyaluronic acid (HA) hydrogels for corneal endothelial tissue engineering is attractive because they can be used as functional cell delivery carriers to help in the reconstruction of damaged areas. The purpose of this study was to investigate the corneal endothelial cytocompatibility and cell delivery performance of porous HA hydrogel biomaterials fabricated at different pre-freezing temperatures. As compared to their counterparts prepared at -80 °C, the HA samples fabricated at higher pre-freezing temperature (i.e., 0 °C) exhibited a larger pore size and higher porosity, thereby leading to lower resistance to glucose permeation. Live/dead assays and gene expression analyses showed that the restricted porous structure of HA carriers decreases the viability and ionic pump function of cultured corneal endothelial cells (CECs). The results also indicated that the porous hydrogel biomaterials fabricated at high pre-freezing temperature seem to be more compatible with rabbit CECs. In an animal model of corneal endothelial dysfunction, the wounded rabbit corneas receiving bioengineered CEC sheets and restricted porous-structured HA carriers demonstrated poor tissue reconstruction. The therapeutic efficacy of cell sheet transplants can be improved by using carrier materials prepared at high pre-freezing temperature. Our findings suggest that the cryogenic operation temperature-mediated pore microstructure of HA carriers plays an important role in corneal endothelial cytocompatibility and cell delivery performance.

Biodegradable and photocrosslinkable polyphosphoester hydrogel

PubMed Central

Li, Qiang; Wang, Jun; Shahani, Shilpa; Sun, Danny D.N.; Sharma, Blanka; Elisseeff, Jennifer H.; Leong, Kam W.

2008-01-01

A new biodegradable, photocrosslinkable and multifunctional macromer, poly(6-aminohexyl propylene phosphate) (PPE-HA)-ACRL, was synthesized by conjugation of acrylate groups to the side chains of PPE-HA. By controlling the synthetic conditions, different weight fractions of acrylate in the macromers were achieved as confirmed by 1H NMR. The hydrogels obtained from PPE-HA-ACRL through photocrosslinking were dominantly elastic. With increasing acrylate contents in the macromers, the hydrogels exhibited a lower swelling ratio and higher mechanical strength. The hydrogels with different crosslinking densities lost between 4.3% and 37.4% of their mass in 84 days when incubated in phosphate-buffered saline at 37 °C. No significant cytotoxicity of the macromers against bone marrow-derived mesenchymal stem cells from goat (GMSC) was observed at a concentration up to 10 mg/ml. Finally, GMSCs encapsulated in the photopolymerized gel maintained their viability when cultured in osteogenic medium for three weeks. Clear mineralization in the hydrogel scaffold was revealed by Von Kossa staining. This study suggests the potential of these biodegradable and photocrosslinkable as injectable tissue engineering scaffolds. PMID:16125222

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

PubMed

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

2015-01-01

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

Hyaluronic Acid and Polyethylene Glycol Hybrid Hydrogel Encapsulating Nanogel with Hemostasis and Sustainable Antibacterial Property for Wound Healing.

PubMed

Zhu, Jie; Li, Faxue; Wang, Xueli; Yu, Jianyong; Wu, Dequn

2018-04-25

Immediate hemorrhage control and anti-infection play important roles in the wound management. Besides, a moist environment is also beneficial for wound healing. Hydrogels are promising materials in urgent hemostasis and drug release. However, hydrogels have the disadvantage of rapid release profiles, leading to the exposure to high drug concentrations. In this study, we constructed hybrid hydrogels with rapid hemostasis and sustainable antibacterial property combining aminoethyl methacrylate hyaluronic acid (HA-AEMA) and methacrylated methoxy polyethylene glycol (mPEG-MA) hybrid hydrogels and chlorhexidine diacetate (CHX)-loaded nanogels. The CHX-loaded nanogels (CLNs) were prepared by the enzyme degradation of CHX-loaded lysine-based hydrogels. The HA-AEMA and mPEG-MA hybrid hydrogel loaded with CLNs (labeled as Gel@CLN) displayed a three-dimensional microporous structure and exhibited excellent swelling, mechanical property, and low cytotoxicity. The Gel@CLN hydrogel showed a prolonged release period of CHX over 240 h and the antibacterial property over 10 days. The hemostasis and wound-healing properties were evaluated in vivo using a mouse model. The results showed that hydrogel had the rapid hemostasis capacity and accelerated wound healing. In summary, CLN-loaded hydrogels may be excellent candidates as hemostasis and anti-infection materials for the wound dressing application.

Injectable In Situ Forming Biodegradable Chitosan-Hyaluronic acid Based Hydrogels for Cartilage Tissue Engineering

PubMed Central

Tan, Huaping; Chu, Constance R.; Payne, Karin; Marra, Kacey G.

2009-01-01

Injectable, biodegradable scaffolds are important biomaterials for tissue engineering and drug delivery. Hydrogels derived from natural polysaccharides are ideal scaffolds as they resemble the extracellular matrices of tissues comprised of various glycosaminoglycans (GAG). Here, we report a new class of biocompatible and biodegradable composite hydrogels derived from water-soluble chitosan and oxidized hyaluronic acid upon mixing, without the addition of a chemical crosslinking agent. The gelation is attributed to the Schiff-base reaction between amino and aldehyde groups of polysaccharide derivatives. In the current work, N-succinyl-chitosan (S-CS) and aldehyde hyaluronic acid (A-HA) were synthesized for preparation of the composite hydrogels. The polysaccharide derivatives and composite hydrogels were characterized by FTIR spectroscopy. The effect of the ratio of S-CS and A-HA on the gelation time, microstructure, surface morphology, equilibrium swelling, compressive modulus, and in vitro degradation of composite hydrogels was examined. The potential of the composite hydrogel as an injectable scaffold was demonstrated by encapsulation of bovine articular chondrocytes within the composite hydrogel matrix in vitro. The results demonstrated that the composite hydrogel supported cell survival and the cells retained chondrocytic morphology. These characteristics provide a potential opportunity to use the injectable, composite hydrogels in tissue engineering applications. PMID:19167750

Formulation Changes Affect Material Properties and Cell Behavior in HA-Based Hydrogels.

PubMed

Lawyer, Thomas; McIntosh, Kristen; Clavijo, Cristian; Potekhina, Lydia; Mann, Brenda K

2012-01-01

To develop and optimize new scaffold materials for tissue engineering applications, it is important to understand how changes to the scaffold affect the cells that will interact with that scaffold. In this study, we used a hyaluronic acid- (HA-) based hydrogel as a synthetic extracellular matrix, containing modified HA (CMHA-S), modified gelatin (Gtn-S), and a crosslinker (PEGda). By varying the concentrations of these components, we were able to change the gelation time, enzymatic degradation, and compressive modulus of the hydrogel. These changes also affected fibroblast spreading within the hydrogels and differentially affected the proliferation and metabolic activity of fibroblasts and mesenchymal stem cells (MSCs). In particular, PEGda concentration had the greatest influence on gelation time, compressive modulus, and cell spreading. MSCs appeared to require a longer period of adjustment to the new microenvironment of the hydrogels than fibroblasts. Fibroblasts were able to proliferate in all formulations over the course of two weeks, but MSCs did not. Metabolic activity changed for each cell type during the two weeks depending on the formulation. These results highlight the importance of determining the effect of matrix composition changes on a particular cell type of interest in order to optimize the formulation for a given application.

Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels

NASA Astrophysics Data System (ADS)

Khetan, Sudhir; Guvendiren, Murat; Legant, Wesley R.; Cohen, Daniel M.; Chen, Christopher S.; Burdick, Jason A.

2013-05-01

Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular traction, independently of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). Moreover, switching the permissive hydrogel to a restrictive state through delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Furthermore, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.

Wide-range stiffness gradient PVA/HA hydrogel to investigate stem cell differentiation behavior.

PubMed

Oh, Se Heang; An, Dan Bi; Kim, Tae Ho; Lee, Jin Ho

2016-04-15

Although stiffness-controllable substrates have been developed to investigate the effect of stiffness on cell behavior and function, the use of separate substrates with different degrees of stiffness, substrates with a narrow range stiffness gradient, toxicity of residues, different surface composition, complex fabrication procedures/devices, and low cell adhesion are still considered as hurdles of conventional techniques. In this study, a cylindrical polyvinyl alcohol (PVA)/hyaluronic acid (HA) hydrogel with a wide-range stiffness gradient (between ∼20kPa and ∼200kPa) and cell adhesiveness was prepared by a liquid nitrogen (LN2)-contacting gradual freezing-thawing method that does not use any additives or specific devices to produce the stiffness gradient hydrogel. From an in vitro cell culture using the stiffness gradient PVA/HA hydrogel, it was observed that human bone marrow mesenchymal stem cells have favorable stiffness ranges for induction of differentiation into specific cell types (∼20kPa for nerve cell, ∼40kPa for muscle cell, ∼80kPa for chondrocyte, and ∼190kPa for osteoblast). The PVA/HA hydrogel with a wide range of stiffness spectrum can be a useful tool for basic studies related with the stem cell differentiation, cell reprogramming, cell migration, and tissue regeneration in terms of substrate stiffness. It is postulated that the stiffness of the extracellular matrix influences cell behavior. To prove this concept, various techniques to prepare substrates with a stiffness gradient have been developed. However, the narrow ranges of stiffness gradient and complex fabrication procedures/devices are still remained as limitations. Herein, we develop a substrate (hydrogel) with a wide-range stiffness gradient using a gradual freezing-thawing method which does not need specific devices to produce a stiffness gradient hydrogel. From cell culture experiments using the hydrogel, it is observed that human bone marrow mesenchymal stem cells have favorable stiffness ranges for induction of differentiation into specific cell types (∼20kPa for nerve, ∼40kPa for muscle, ∼80kPa for cartilage, and ∼190kPa for bone in our hydrogel system). Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Injectable hyperbranched poly(β-amino ester) hydrogels with on-demand degradation profiles to match wound healing processes.

PubMed

Xu, Qian; Guo, Linru; A, Sigen; Gao, Yongsheng; Zhou, Dezhong; Greiser, Udo; Creagh-Flynn, Jack; Zhang, Hong; Dong, Yixiao; Cutlar, Lara; Wang, Fagang; Liu, Wenguang; Wang, Wei; Wang, Wenxin

2018-02-28

Adjusting biomaterial degradation profiles to match tissue regeneration is a challenging issue. Herein, biodegradable hyperbranched poly(β-amino ester)s (HP-PBAEs) were designed and synthesized via "A2 + B4" Michael addition polymerization, and displayed fast gelation with thiolated hyaluronic acid (HA-SH) via a "click" thiol-ene reaction. HP-PBAE/HA-SH hydrogels showed tunable degradation profiles both in vitro and in vivo using diamines with different alkyl chain lengths and poly(ethylene glycol) diacrylates with varied PEG spacers. The hydrogels with optimized degradation profiles encapsulating ADSCs were used as injectable hydrogels to treat two different types of humanized excisional wounds - acute wounds with faster healing rates and diabetic wounds with slower healing and neo-tissue formation. The fast-degrading hydrogel showed accelerated wound closure in acute wounds, while the slow-degrading hydrogel showed better wound healing for diabetic wounds. The results demonstrate that the new HP-PBAE-based hydrogel in combination with ADSCs can be used as a well-controlled biodegradable skin substitute, which demonstrates a promising approach in the treatment of various types of skin wounds.

Rheological, mechanical and degradable properties of injectable chitosan/silk fibroin/hydroxyapatite/glycerophosphate hydrogels.

PubMed

Wu, Jingjing; Liu, Jiaoyan; Shi, Yanmei; Wan, Ying

2016-12-01

Silk fibroin (SF) and hydroxyapatite (HA) were incorporated into chitosan/glycerophosphate (GP) system to prepare new types of hydrogels. The formulated chitosan/SF/GP and chitosan/SF/HA/GP solutions were found to be injectable at room temperature, and able to form into hydrogels at near-physiological temperature and pH. Rheological measurements showed that elastic modulus of certain chitosan/SF/GP and chitosan/SF/HA/GP gels could reach around 1.8 and 15kPa, respectively, and was much higher than their respective viscous modulus. Compressive measurements revealed that some chitosan/SF/GP and chitosan/SF/HA/GP gels had 8 and 20-fold modulus and strength higher than the chitosan/GP gel, respectively, confirming that compressive properties of these gels were greatly improved. Results obtained from in vivo degradation demonstrated that degradation endurance of the optimized chitosan/SF/GP and chitosan/SF/HA/GP gels was significantly enhanced as compared to the chitosan/GP gel, and the degradation rate of the gels could be regulated by the SF component alone or by the combination of SF and HA components. Copyright © 2016 Elsevier Ltd. All rights reserved.

78 FR 9884 - Approval of Subzone Status; Zimmer Manufacturing BV; Ponce, Puerto Rico

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-12

...; Zimmer Manufacturing BV; Ponce, Puerto Rico Pursuant to its authority under the Foreign-Trade Zones Act... subzone at the facility of Zimmer Manufacturing BV located in Ponce, Puerto Rico (FTZ Docket B-81-2012... hereby approves subzone status at the facility of Zimmer Manufacturing BV located in Ponce, Puerto Rico...

Surface-modified silk hydrogel containing hydroxyapatite nanoparticle with hyaluronic acid-dopamine conjugate.

PubMed

Kim, Hyung Hwan; Park, Jong Bo; Kang, Min Ji; Park, Young Hwan

2014-09-01

Silk fibroin/hydroxyapatite (SF/HAp) composite hydrogels were fabricated in this study, having different HAp contents (0-33 wt%) in SF matrix hydrogel. Surface modification of HAp nanoparticle with hyaluronic acid (HA)-dopamine (DA) conjugate improved a dispersibility of HAp in aqueous SF solution due to its negatively charged surface and therefore, fabrication of the SF composite hydrogel having HAp nanoparticles inside could be possible. Zeta potential of surface-modified HAP was examined by ELS. It demonstrates that surface of HAp was well modified to a negative charge with HA-DA. Morphological structure of SF hydrogel containing surface-modified HAp was examined by FE-SEM for analyzing pore structure of hydrogel and deposition of HAp nanoparticle in SF hydrogel. It was found that HAp nanoparticles were uniformly deposited on the pore wall of SF hydrogel. Structural characteristics of SF/HAp composite hydrogel was performed using X-ray diffraction and FT-IR analysis. It was found that β-sheet crystal conformation of SF was significantly influenced by the HAp content during gelation of a mixture of SF and HAp. As a result of MTT assay, the SF/HAp composite hydrogel showed excellent cell proliferation ability. Therefore, it is expected that SF hydrogel containing HAp nanoparticles has a high potential as bone regeneration scaffold. Copyright © 2014 Elsevier B.V. All rights reserved.

A tunable hydrogel system for long-term release of cell-secreted cytokines and bioprinted in situ wound cell delivery.

PubMed

Skardal, Aleksander; Murphy, Sean V; Crowell, Kathryn; Mack, David; Atala, Anthony; Soker, Shay

2017-10-01

For many cellular therapies being evaluated in preclinical and clinical trials, the mechanisms behind their therapeutic effects appear to be the secretion of growth factors and cytokines, also known as paracrine activity. Often, delivered cells are transient, and half-lives of the growth factors that they secrete are short, limiting their long-term effectiveness. The goal of this study was to optimize a hydrogel system capable of in situ cell delivery that could sequester and release growth factors secreted from those cells after the cells were no longer present. Here, we demonstrate the use of a fast photocross-linkable heparin-conjugated hyaluronic acid (HA-HP) hydrogel as a cell delivery vehicle for sustained growth factor release, which extends paracrine activity. The hydrogel could be modulated through cross-linking geometries and heparinization to support sustained release proteins and heparin-binding growth factors. To test the hydrogel in vivo, we used it to deliver amniotic fluid-derived stem (AFS) cells, which are known to secrete cytokines and growth factors, in full thickness skin wounds in a nu/nu murine model. Despite transience of the AFS cells in vivo, the HA-HP hydrogel with AFS cells improved wound closure and reepithelialization and increased vascularization and production of extracellular matrix in vivo. These results suggest that HA-HP hydrogel has the potential to prolong the paracrine activity of cells, thereby increasing their therapeutic effectiveness in wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1986-2000, 2017. © 2016 Wiley Periodicals, Inc.

Characterization of protein release from photocrosslinkable hyaluronic acid-polyethylene glycol hydrogel tissue engineering scaffolds.

PubMed

Leach, Jennie B; Schmidt, Christine E

2005-01-01

The goal of this work was to utilize the naturally derived bioactive polymer hyaluronic acid (HA) to create a combination tissue engineering scaffold and protein delivery device. HA is a non-immunogenic, non-adhesive glycosaminoglycan that plays significant roles in several cellular processes, including angiogenesis and the regulation of inflammation. In previous work, we created photopolymerizable glycidyl methacrylate-hyaluronic acid (GMHA) hydrogels that had controlled degradation rates, were cytocompatible, and were able to be modified with peptide moieties. In the present studies, we characterized the release of a model protein, bovine serum albumin (BSA), from GMHA and GMHA-polyethylene glycol (PEG) hydrogels. Although BSA could be released rapidly (> 60% within 6 h) from 1% GMHA hydrogels, we found that increasing either the GMHA or the PEG concentrations could lengthen the duration of protein delivery. Preliminary size exclusion chromatography studies indicated that the released BSA was almost entirely in its native monomeric form. Lastly, protein release was extended to several weeks by suspending BSA-poly(lactic-co-glycolic acid) microspheres within the hydrogel bulk. These initial studies indicate that the naturally derived biopolymer HA can be employed to design novel photopolymerizable composites that are suitable for delivering stable proteins from scaffolding in tissue engineering applications.

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

NASA Astrophysics Data System (ADS)

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

2011-07-01

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

Wound healing potential of a dimeric InlB variant analyzed by in vitro experiments on re-epithelialization of human skin models.

PubMed

Kolditz, F; Krausze, J; Heinz, D W; Niemann, H H; Müller-Goymann, C C

2014-02-01

A constitutively dimeric truncated variant of internalin B (InlB321-CD), acting as stimulator of the receptor tyrosine kinase MET, was tested for dermal wound-healing potential. Due to a lack of the endogenous MET agonist HGF/SF in chronic wounds, HGF/SF substitution by an InlB321-CD-loaded hydrogel might be beneficial in chronic wound therapy. In this study, InlB321-CD in solution and incorporated in a hydrogel was tested for mitogenic effects on immortalized human dermal keratinocytes (HaCaT) with an MTT assay. Cell migration was investigated with a scratch assay on primary keratinocytes (PHK) and on HaCaT. For the latter, scratching needed to be mitomycin C-controlled. InlB321-CD effects on a model of human skin were analyzed histologically with respect to viability. InlB321-CD led to dose-dependent proliferative effects on HaCaT cells whereas the equimolar dose of monomeric InlB321 did not. Upon hydrogel incorporation of InlB321-CD its mitogenic activity for HaCaT cells was maintained thus confirming the hydrogel as a promising drug delivery system. Motogenic effects were shown on both HaCaT and PHK cells. InlB321-CD neither possesses cytotoxic effects on the viability of a human skin model nor alters its organotypic cell morphology. Copyright © 2013 Elsevier B.V. All rights reserved.

Synthesis and characterization of a novel hyaluronic acid hydrogel.

PubMed

Zhao, X

2006-01-01

Hyaluronic acid (hyaluronan, HA) has many medical applications as a biomaterial. To enhance its biostability, a novel hydrogel of cross-linked hyaluronic acid was prepared using a double cross-linking process, which involves building cross-linkages between hydroxyl group pairs and carboxyl group pairs. The present study explored a number of cross-linking processes in order to obtain different degrees of cross-linking, which were evaluated by the measurement of water absorption capacity as an index of the gel network density. To gain a better understanding of the stability of the gel, the chemical structure and particularly the rheological behaviour of the cross-linked HA, which included the influences of factors, such as degree of cross-linking, HA concentration and gel particle size, were investigated. The in vitro biostability against hyaluronidase and free radical degradation was tested to show that the cross-linked hydrogel had improved resistance to in vitro hyaluronidase and free radical degradation.

Microscale Characterization of the Viscoelastic Properties of Hydrogel Biomaterials using Dual-Mode Ultrasound Elastography

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-05-01

Characterization of the microscale mechanical properties of biomaterials is a key challenge in the field of mechanobiology. Dual-mode ultrasound elastography (DUE) uses high frequency focused ultrasound to induce compression in a sample, combined with interleaved ultrasound imaging to measure the resulting deformation. This technique can be used to non-invasively perform creep testing on hydrogel biomaterials to characterize their viscoelastic properties. DUE was applied to a range of hydrogel constructs consisting of either hydroxyapatite (HA)-doped agarose, HA-collagen, HA-fibrin, or preosteoblast-seeded collagen constructs. DUE provided spatial and temporal mapping of local and bulk displacements and strains at high resolution. Hydrogel materials exhibited characteristic creep behavior, and the maximum strain and residual strain were both material- and concentration-dependent. Burger's viscoelastic model was used to extract characteristic parameters describing material behavior. Increased protein concentration resulted in greater stiffness and viscosity, but did not affect the viscoelastic time constant of acellular constructs. Collagen constructs exhibited significantly higher modulus and viscosity than fibrin constructs. Cell-seeded collagen constructs became stiffer with altered mechanical behavior as they developed over time. Importantly, DUE also provides insight into the spatial variation of viscoelastic properties at sub-millimeter resolution, allowing interrogation of the interior of constructs. DUE presents a novel technique for non-invasively characterizing hydrogel materials at the microscale, and therefore may have unique utility in the study of mechanobiology and the characterization of hydrogel biomaterials. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sulfobetaine as a zwitterionic mediator for 3D hydroxyapatite mineralization

PubMed Central

Liu, Pingsheng; Song, Jie

2013-01-01

Both positively and negatively charged residues play pivotal roles in recruiting precursor ions or ion clusters, and lowering interfacial energy in natural biomineralization process. Synergistic utilization of opposite charges, however, has rarely been implemented in the design of cytocompatible synthetic scaffolds promoting hydroxyapatite (HA)-mineralization and osteointegration. We report the use of cytocompatible zwitterionic sulfobetaine ligands to enable 3-dimensional in vitro mineralization of HA across covalently crosslinked hydrogels. The overall charge-neutral zwitterionic hydrogel effectively recruited oppositely charged precursor ions while overcame excessive swelling exhibited by anionic and cationic hydrogels under physiological conditions, resulting in denser and structurally well-integrated mineralized composites. Further controls over the size, content, and spatial distribution of the mineral domains within the zwitterionic hydrogel are accomplished by facile adjustments of hydrogel crosslinking densities and the supersaturation rate governing heterogeneous mineral nucleation and growth. These findings should inspire many creative uses of zwitterionic polymers and polymer coatings for skeletal tissue repair and regeneration. PMID:23332320

Sulfobetaine as a zwitterionic mediator for 3D hydroxyapatite mineralization.

PubMed

Liu, Pingsheng; Song, Jie

2013-03-01

Both positively and negatively charged residues play pivotal roles in recruiting precursor ions or ion clusters, and lowering interfacial energy in natural biomineralization process. Synergistic utilization of opposite charges, however, has rarely been implemented in the design of cytocompatible synthetic scaffolds promoting hydroxyapatite (HA)-mineralization and osteointegration. We report the use of cytocompatible zwitterionic sulfobetaine ligands to enable 3-dimensional in vitro mineralization of HA across covalently crosslinked hydrogels. The overall charge-neutral zwitterionic hydrogel effectively recruited oppositely charged precursor ions while overcame excessive swelling exhibited by anionic and cationic hydrogels under physiological conditions, resulting in denser and structurally well-integrated mineralized composites. Further controls over the size, content, and spatial distribution of the mineral domains within the zwitterionic hydrogel are accomplished by facile adjustments of hydrogel crosslinking densities and the supersaturation rate governing heterogeneous mineral nucleation and growth. These findings should inspire many creative uses of zwitterionic polymers and polymer coatings for skeletal tissue repair and regeneration. Copyright © 2012 Elsevier Ltd. All rights reserved.

In situ cross-linkable high molecular weight hyaluronan-bisphosphonate conjugate for localized delivery and cell-specific targeting: a hydrogel linked prodrug approach.

PubMed

Varghese, Oommen P; Sun, Weilun; Hilborn, Jöns; Ossipov, Dmitri A

2009-07-01

We present here a novel synthesis route to functionalize high molecular weight hyaluronan (HMW-HA) with a hydrazide group and a bioactive ligand, namely bisphosphonate (BP). For this purpose, a new symmetrical self-immolative biscarbazate linker has been devised. The hydrazide group was used to form hydrazone cross-linked hydrogel upon treating with previously described aldehyde modified hyaluronan. The 1:1 weight ratio of these two polymers gave hydrogel in less than 30 s. In this communication we present the first in vitro results showing that even though HA can target CD44 positive cancer cells (HCT-116), receptor mediated endocytosis could only occur by cleavage of high molecular weight HA with an ubiquitous enzyme, hyaluronidase (Hase). The cancer cells are known to overexpress CD44 receptors and also increase the hyaluronidase activity in vivo. Thus the pro-drug design, based on drug conjugation to HMW-HA, represents a new drug delivery platform where the drug potency is triggered by Hase mediated degradation of the HA-drug conjugate. We have successfully demonstrated that the cross-linkable HA-BP conjugate first undergoes Hase-mediated scission to the fragments of suitable sizes so as to be internalized by CD44 positive cells. The specificity of this targeting was proven by comparing the results with less CD44 positive HEK-293T cells. The localized delivery of such drugs at the surgical resection site opens up avenues to control tumor recurrence after removal of the tumor. In the form of hydrogel it would prevent systemic exposure of the drug and would allow its controlled release.

In vivo remineralization of dentin using an agarose hydrogel biomimetic mineralization system

NASA Astrophysics Data System (ADS)

Han, Min; Li, Quan-Li; Cao, Ying; Fang, Hui; Xia, Rong; Zhang, Zhi-Hong

2017-02-01

A novel agarose hydrogel biomimetic mineralization system loaded with calcium and phosphate was used to remineralize dentin and induce the oriented densely parallel packed HA layer on defective dentin surface in vivo in a rabbit model. Firstly, the enamel of the labial surface of rabbits’ incisor was removed and the dentin was exposed to oral environment. Secondly, the hydrogel biomimetic mineralization system was applied to the exposed dentin surface by using a custom tray. Finally, the teeth were extracted and evaluated by scanning electron microscopy, X-ray diffraction, and nanoindentation test after a certain time of mineralization intervals. The regenerated tissue on the dentin surface was composed of highly organised HA crystals. Densely packed along the c axis, these newly precipitated HA crystals were perpendicular to the underlying dental surface with a tight bond. The demineralized dentin was remineralized and dentinal tubules were occluded by the grown HA crystals. The nanohardness and elastic modulus of the regenerated tissue were similar to natural dentin. The results indicated a potential clinical use for repairing dentin-exposed related diseases, such as erosion, wear, and dentin hypersensitivity.

Photocrosslinked Tyramine-Substituted Hyaluronate Hydrogels with Tunable Mechanical Properties Improve Immediate Tissue‐Hydrogel Interfacial Strength in Articular Cartilage

PubMed Central

Donnelly, Patrick E.; Chen, Tony; Finch, Anthony; Brial, Caroline; Maher, Suzanne A.; Torzilli, Peter A.

2017-01-01

Articular cartilage lacks the ability to self-repair and a permanent solution for cartilage repair remains elusive. Hydrogel implantation is a promising technique for cartilage repair; however for the technique to be successful hydrogels must interface with the surrounding tissue. The objective of this study was to investigate the tunability of mechanical properties in a hydrogel system using a phenol-substituted polymer, tyramine-substituted hyaluronate (TA-HA), and to determine if the hydrogels could form an interface with cartilage. We hypothesized that tyramine moieties on hyaluronate could crosslink to aromatic amino acids in the cartilage extracellular matrix. Ultraviolet (UV) light and a riboflavin photosensitizer were used to create a hydrogel by tyramine self‐crosslinking. The gel mechanical properties were tuned by varying riboflavin concentration, TA-HA concentration, and UV exposure time. Hydrogels formed with a minimum of 2.5 min of UV exposure. The compressive modulus varied from 5–16 kPa. Fluorescence spectroscopy analysis found differences in dityramine content. Cyanine-3 labelled tyramide reactivity at the surface of cartilage was dependent on the presence of riboflavin and UV exposure time. Hydrogels fabricated within articular cartilage defects had increasing peak interfacial shear stress at the cartilage-hydrogel interface with increasing UV exposure time, reaching a maximum shear stress 3.5× greater than a press‐fit control. Our results found that phenol-substituted polymer/riboflavin systems can be used to fabricate hydrogels with tunable mechanical properties and can interface with the surface tissue, such as articular cartilage. PMID:28134036

In vitro epithelial differentiation of human induced pluripotent stem cells for vocal fold tissue engineering.

PubMed

Imaizumi, Mitsuyoshi; Sato, Yuka; Yang, David T; Thibeault, Susan L

2013-12-01

We determined the feasibility and optimization of differentiating human induced pluripotent stem cells (hiPS) into nonkeratinized stratified squamous epithelial cells for vocal fold engineering. hiPS were cultured and assessed for differentiation in 3 conditions: a 3-dimensional (3D) hyaluronic acid (HA) hydrogel scaffold, a 3D HA hydrogel scaffold with epidermal growth factor (EGF), and a 3D HA hydrogel scaffold cocultured with human vocal fold fibroblasts (hVFF). After 1, 2, and 4 weeks of cultivation, hiPS were selected for histology, immunohistochemistry, and/or transcript expression analysis. At 4 weeks, hiPS cultivated with hVFF or with EGF had significantly decreased levels of Oct 3/4, indicating loss of pluripotency. Immunofluorescence revealed the presence of pancytokeratin and of cytokeratin (CK) 13 and 14 epithelial-associated proteins at 4 weeks after cultivation in hiPS EGF and hiPS hVFF cultures. The transcript expression level of CK14 was significantly increased for hiPS hVFF cultures only and was measured concomitantly with cell morphology that was clearly cohesive and displayed a degree of nuclear polarity suggestive of epithelial differentiation. We found that hiPS cultivated in 3D HA hydrogel with hVFF demonstrated the most robust conversion evidence to date of epithelial differentiation. Further work is necessary to focus on amplification of these progenitors for application in vocal fold regenerative biology.

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

PubMed

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

2017-11-01

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

Self-assembled high-strength hydroxyapatite/graphene oxide/chitosan composite hydrogel for bone tissue engineering.

PubMed

Yu, Peng; Bao, Rui-Ying; Shi, Xiao-Jun; Yang, Wei; Yang, Ming-Bo

2017-01-02

Graphene hydrogel has shown greatly potentials in bone tissue engineering recently, but it is relatively weak in the practical use. Here we report a facile method to synthesize high strength composite graphene hydrogel. Graphene oxide (GO), hydroxyapatite (HA) nanoparticles (NPs) and chitosan (CS) self-assemble into a 3-dimensional hydrogel with the assistance of crosslinking agent genipin (GNP) for CS and reducing agent sodium ascorbate (NaVC) for GO simultaneously. The dense and oriented microstructure of the resulted composite gel endows it with high mechanical strength, high fixing capacity of HA and high porosity. These properties together with the good biocompatibility make the ternary composite gel a promising material for bone tissue engineering. Such a simultaneous crosslinking and reduction strategy can also be applied to produce a variety of 3D graphene-polymer based nanocomposites for biomaterials, energy storage materials and adsorbent materials. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alginate/hyaluronic acid hydrogel delivery system characteristics regulate the differentiation of periodontal ligament stem cells toward chondrogenic lineage.

PubMed

Ansari, Sahar; Diniz, Ivana M; Chen, Chider; Aghaloo, Tara; Wu, Benjamin M; Shi, Songtao; Moshaverinia, Alireza

2017-09-15

Cartilage tissue regeneration often presents a challenging clinical situation. Recently, it has been shown that Periodontal Ligament Stem Cells (PDLSCs) possess high chondrogenic differentiation capacity. In this study, we developed a stem cell delivery system based on alginate/hyaluronic acid (HA) loaded with TGF-β1 ligand, encapsulating PDLSCs; and investigated the chondrogenic differentiation of encapsulated cells in alginate/HA hydrogel microspheres in vitro and in vivo. The results showed that PDLSCs, as well as human bone marrow mesenchymal stem cells (hBMMSCs), as the positive control, were stained positive for both toluidine blue and alcian blue staining, while exhibiting high levels of gene expression related to chondrogenesis (Col II, Aggrecan and Sox-9), as assessed via qPCR. The quantitative PCR analyses exhibited that the chondrogenic differentiation of encapsulated MSCs can be regulated by the modulus of elasticity of hydrogel delivery system, confirming the vital role of the microenvironment, and the presence of inductive signals for viability and differentiation of MSCs. In vivo, histological and immunofluorescence staining for chondrogenic specific protein markers confirmed ectopic cartilage-like tissue regeneration inside transplanted hydrogels. PDLSCs presented significantly greater capability for chondrogenic differentiation than hBMMSCs (P < 0.05). Altogether, our findings confirmed that alginate/HA hydrogels encapsulating PDLSCs are a promising candidate for cartilage regeneration.

Differentiation potential of human adipose stem cells bioprinted with hyaluronic acid/gelatin-based bioink through microextrusion and visible light-initiated crosslinking.

PubMed

Sakai, Shinji; Ohi, Hiromi; Hotta, Tomoki; Kamei, Hidenori; Taya, Masahito

2018-02-01

Bioprinting has a great potential to fabricate three-dimensional (3D) functional tissues and organs. In particular, the technique enables fabrication of 3D constructs containing stem cells while maintaining cell proliferation and differentiation abilities, which is believed to be promising in the fields of tissue engineering and regenerative medicine. We aimed to demonstrate the utility of the bioprinting technique to create hydrogel constructs consisting of hyaluronic acid (HA) and gelatin derivatives through irradiation by visible light to fabricate 3D constructs containing human adipose stem cells (hADSCs). The hydrogel was obtained from a solution of HA and gelatin derivatives possessing phenolic hydroxyl moieties in the presence of ruthenium(II) tris-bipyridyl dication and sodium ammonium persulfate. hADSCs enclosed in the bioprinted hydrogel construct elongated and proliferated in the hydrogel. In addition, their differentiation potential was confirmed by examining the expression of pluripotency marker genes and cell surface marker proteins, and differentiation to adipocytes in adipogenic differentiation medium. Our results demonstrate the great potential of the bioprinting method and the resultant hADSC-laden HA/gelatin constructs for applications in tissue engineering and regenerative medicine. © 2017 Wiley Periodicals, Inc.

Injectable hyperbranched poly(β-amino ester) hydrogels with on-demand degradation profiles to match wound healing processes† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc03913a

PubMed Central

Xu, Qian; Guo, Linru; A, Sigen; Gao, Yongsheng; Zhou, Dezhong; Greiser, Udo; Creagh-Flynn, Jack; Zhang, Hong; Dong, Yixiao; Cutlar, Lara; Wang, Fagang; Liu, Wenguang

2018-01-01

Adjusting biomaterial degradation profiles to match tissue regeneration is a challenging issue. Herein, biodegradable hyperbranched poly(β-amino ester)s (HP-PBAEs) were designed and synthesized via “A2 + B4” Michael addition polymerization, and displayed fast gelation with thiolated hyaluronic acid (HA-SH) via a “click” thiol–ene reaction. HP-PBAE/HA-SH hydrogels showed tunable degradation profiles both in vitro and in vivo using diamines with different alkyl chain lengths and poly(ethylene glycol) diacrylates with varied PEG spacers. The hydrogels with optimized degradation profiles encapsulating ADSCs were used as injectable hydrogels to treat two different types of humanized excisional wounds – acute wounds with faster healing rates and diabetic wounds with slower healing and neo-tissue formation. The fast-degrading hydrogel showed accelerated wound closure in acute wounds, while the slow-degrading hydrogel showed better wound healing for diabetic wounds. The results demonstrate that the new HP-PBAE-based hydrogel in combination with ADSCs can be used as a well-controlled biodegradable skin substitute, which demonstrates a promising approach in the treatment of various types of skin wounds. PMID:29719691

The Impact of HA Oligomer Content on Physical, Mechanical, and Biologic Properties of Divinyl Sulfone-Crosslinked HA Hydrogels

PubMed Central

Ibrahim, Samir; Kang, Qian K; Ramamurthi, Anand

2009-01-01

In recent studies, we showed that exogenous hyaluronic acid oligomers (HA-o) stimulate functional endothelialization, though native long-chain HA is more bioinert and possibly more biocompatible. Thus, in this study, hydrogels containing high molecular weight (HMW) HA (1×106 Da) and HA oligomer mixtures (HA-o: 0.75–10 kDa) were created by crosslinking with divinyl sulfone (DVS). The incorporation of HA oligomers was found to compromise the physical and mechanical properties of the gels (rheology, apparent crosslinking density, swelling ratio, degradation) and to very mildly enhance inflammatory cell recruitment in vivo; increasing the DVS crosslinker content within the gels in general, had the opposite effect, though the relatively high concentration of DVS within these gels (necessary to create a solid gel) also stimulated a mild sub-cutaneous inflammatory response in vivo and VCAM-1 expression by ECs cultured atop; ICAM-expression levels remained very low irrespective extent of DVS crosslinking or HA-o content. The greatest EC attachment and proliferation (MTT assay) was observed on gels that contained the highest amount of HA-o. The study shows that the beneficial EC response to HA oligomers and biocompatibility of HA is mostly unaltered by their chemical derivatization and crosslinking into a hydrogel. However, the study also demonstrates that the relatively high concentrations of DVS, necessary to create solid gels, compromises their biocompatibility. Moreover, the poor mechanics of even these heavily crosslinked gels, in the context of vascular implantation, necessitates the investigation of other, more appropriate crosslinking agents. Alternately, the outcomes of this study may be used to guide an approach based on chemical immobilization and controlled surface-presentation of both bioactive HA oligomers and more biocompatible HMW HAon synthetic or tissue engineered grafts already in use, without the use of a crosslinker, so that improved, predictable, and functional endothelialization can be achieved, and the need to create a mechanically compliant biomaterial for standalone use, circumvented. PMID:20186732

The influence of hyaluronic acid hydrogel crosslinking density and macromolecular diffusivity on human MSC chondrogenesis and hypertrophy.

PubMed

Bian, Liming; Hou, Chieh; Tous, Elena; Rai, Reena; Mauck, Robert L; Burdick, Jason A

2013-01-01

Hyaluronic acid (HA) hydrogels formed via photocrosslinking provide stable 3D hydrogel environments that support the chondrogenesis of mesenchymal stem cells (MSCs). Crosslinking density has a significant impact on the physical properties of hydrogels, including their mechanical stiffness and macromolecular diffusivity. Variations in the HA hydrogel crosslinking density can be obtained by either changes in the HA macromer concentration (1, 3, or 5% w/v at 15 min exposure) or the extent of reaction through light exposure time (5% w/v at 5, 10, or 15 min). In this work, increased crosslinking by either method resulted in an overall decrease in cartilage matrix content and more restricted matrix distribution. Increased crosslinking also promoted hypertrophic differentiation of the chondrogenically induced MSCs, resulting in more matrix calcification in vitro. For example, type X collagen expression in the high crosslinking density 5% 15 min group was ~156 and 285% higher when compared to the low crosslinking density 1% 15 min and 5% 5 min groups on day 42, respectively. Supplementation with inhibitors of the small GTPase pathway involved in cytoskeletal tension or myosin II had no effect on hypertrophic differentiation and matrix calcification, indicating that the differential response is unlikely to be related to force-sensing mechanotransduction mechanisms. When implanted subcutaneously in nude mice, higher crosslinking density again resulted in reduced cartilage matrix content, restricted matrix distribution, and increased matrix calcification. This study demonstrates that hydrogel properties mediated through alterations in crosslinking density must be considered in the context of the hypertrophic differentiation of chondrogenically induced MSCs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hybrid Protein–Glycosaminoglycan Hydrogels Promote Chondrogenic Stem Cell Differentiation

PubMed Central

2017-01-01

Gelatin–hyaluronic acid (Gel–HA) hybrid hydrogels have been proposed as matrices for tissue engineering because of their ability to mimic the architecture of the extracellular matrix. Our aim was to explore whether tyramine conjugates of Gel and HA, producing injectable hydrogels, are able to induce a particular phenotype of encapsulated human mesenchymal stem cells without the need for growth factors. While pure Gel allowed good cell adhesion without remarkable differentiation and pure HA triggered chondrogenic differentiation without cell spreading, the hybrids, especially those rich in HA, promoted chondrogenic differentiation as well as cell proliferation and adhesion. Secretion of chondrogenic markers such as aggrecan, SOX-9, collagen type II, and glycosaminoglycans was observed, whereas osteogenic, myogenic, and adipogenic markers (RUNX2, sarcomeric myosin, and lipoproteinlipase, respectively) were not present after 2 weeks in the growth medium. The most promising matrix for chondrogenesis seems to be a mixture containing 70% HA and 30% Gel as it is the material with the best mechanical properties from all compositions tested here, and at the same time, it provides an environment suitable for balanced cell adhesion and chondrogenic differentiation. Thus, it represents a system that has a high potential to be used as the injectable material for cartilage regeneration therapies. PMID:29214232

Mechano-responsive hydrogels crosslinked by reactive block copolymer micelles

NASA Astrophysics Data System (ADS)

Xiao, Longxi

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

Biomimetic Hydrogels Incorporating Polymeric Cell-Adhesive Peptide to Promote the 3D Assembly of Tumoroids

PubMed Central

Hao, Ying; Zerdoum, Aidan B.; Stuffer, Alexander J.; Rajasekaran, Ayyappan K.; Jia, Xinqiao

2016-01-01

Towards the goal of establishing physiologically relevant in vitro tumor models, we synthesized and characterized a biomimetic hydrogel using thiolated hyaluronic acid (HA-SH) and an acrylated copolymer carrying multiple copies of cell adhesive peptide (PolyRGD-AC). PolyRGD-AC was derived from a random copolymer of tert-butyl methacrylate (tBMA) and oligomeric (ethylene glycol) methacrylate (OEGMA), synthesized via atom transfer radical polymerization (ATRP). Acid hydrolysis of tert-butyl moieties revealed the carboxylates, through which acrylate groups were installed. Partial modification of the acrylate groups with a cysteine-containing RGD peptide generated PolyRGD-AC. When PolyRGD-AC was mixed with HA-SH under physiological conditions, a macroscopic hydrogel with an average elastic modulus of 630 Pa was produced. LNCaP prostate cancer cells encapsulated in HA-PolyRGD gels as dispersed single cells formed multicellular tumoroids by day 4 and reached an average diameter of ~95 μm by day 28. Cells in these structures were viable, formed cell-cell contacts through E-cadherin (E-CAD and displayed cortical organization of F-actin. Compared to the control gels prepared using PolyRDG, multivalent presentation of the RGD signal in the HA matrix increased cellular metabolism, promoted the development of larger tumoroids and enhanced the expression of E-CAD and integrins. Overall, hydrogels with multivalently immobilized RGD is a promising 3D culture platform for dissecting principles of tumorigenesis and for screening anticancer drugs. PMID:27723964

Evaluation of BSA protein release from hollow hydroxyapatite microspheres into PEG hydrogel

PubMed Central

Fu, Hailuo; Rahaman, Mohamed N.; Brown, Roger F.; Day, Delbert E.

2013-01-01

Implants that simultaneously function as an osteoconductive matrix and as a device for local drug or growth factor delivery could provide an attractive system for bone regeneration. In our previous work, we prepared hollow hydroxyapatite (abbreviated HA) microspheres with a high surface area, mesoporous shell wall and studied the release of a model protein, bovine serum albumin (BSA), from the microspheres into phosphate-buffered saline (PBS). The present work is an extension of our previous work to study the release of BSA from similar HA microspheres into a biocompatible hydrogel, poly(ethylene glycol) (PEG). BSA-loaded HA microspheres were placed in a PEG solution which was rapidly gelled using ultraviolet radiation. The BSA release rate into the PEG hydrogel, measured using a spectrophotometric method, was slower than into PBS, and it was dependent on the initial BSA loading and on the microstructure of the microsphere shell wall. A total of 35–40% of the BSA initially loaded into the microspheres was released into PEG over ~14 days. The results indicate that these hollow HA microspheres have promising potential as an osteoconductive device for local drug or growth factor delivery in bone regeneration and in the treatment of bone diseases. PMID:23498254

Effects of matrix composition, microstructure, and viscoelasticity on the behaviors of vocal fold fibroblasts cultured in three-dimensional hydrogel networks.

PubMed

Farran, Alexandra J E; Teller, Sean S; Jha, Amit K; Jiao, Tong; Hule, Rohan A; Clifton, Rodney J; Pochan, Darrin P; Duncan, Randall L; Jia, Xinqiao

2010-04-01

Vocal fold diseases and disorders are difficult to treat surgically or therapeutically. Tissue engineering offers an alternative strategy for the restoration of functional vocal folds. As a first step toward vocal fold tissue engineering, we investigated the responses of primary vocal fold fibroblasts (PVFFs) to two types of collagen and hyaluronic acid (HA)-based hydrogels that are compositionally similar, but structurally variable and mechanically different. Type A hydrogels were composed of mature collagen fibers reinforced by oxidized HA, whereas type B hydrogels contained immature collagen fibrils interpenetrated in an amorphous, covalently cross-linked HA matrix. PVFFs encapsulated in either matrix adopted a fibroblastic morphology and expressed genes related to important extracellular matrix proteins. DNA analysis indicated a linear growth profile for cells encapsulated in type B gels from day 0 to 21, in contrast to an initial dormant, nonproliferative period from day 0 to 3 experienced by cells in type A gels. At the end of the culture, similar DNA content was detected in both types of constructs. A reduction in collagen content was observed for both types of constructs after 28 days of culture, with type A constructs generally retaining higher amounts of collagen than type B constructs. The HA content in the constructs decreased steadily throughout the culture, with type A constructs consistently exhibiting less HA than type B constructs. Using the torsional wave analysis, we found that the elastic moduli for type A constructs decreased sharply during the first week of culture, followed by 2 weeks of matrix stabilization without significant changes in matrix stiffness. Conversely, the elastic modulus for type B constructs increased moderately over time. It is postulated that PVFFs residing in gels alter the matrix organization, chemical compositions, and viscoelasticity through cell-mediated remodeling processes.

Hyaluronic Acid/Collagen Hydrogel as an Alternative to Alginate for Long-Term Immunoprotected Islet Transplantation.

PubMed

Harrington, Stephen; Williams, Janette; Rawal, Sonia; Ramachandran, Karthik; Stehno-Bittel, Lisa

2017-10-01

Alginate has long been the material of choice for immunoprotection of islets due to its low cost and ability to easily form microspheres. Unfortunately, this seaweed-derived material is notoriously prone to fibrotic overgrowth in vivo, resulting in premature graft failure. The purpose of this study was to test an alternative, hyaluronic acid (HA-COL), for in vitro function, viability, and allogeneic islet transplant outcomes in diabetic rats. In vitro studies indicated that the HA-COL gel had diffusion characteristics that would allow small molecules such as glucose and insulin to enter and exit the gel, whereas larger molecules (70 and 500 kDa dextrans) were impeded from diffusing past the gel edge in 24 h. Islets encapsulated in HA-COL hydrogel showed significantly improved in vitro viability over unencapsulated islets and retained their morphology and glucose sensitivity for 28 days. When unencapsulated allogeneic islet transplants were administered to the omentum of outbred rats, they initially were normoglycemic, but by 11 days returned to hyperglycemia. Immunohistological examination of the grafts and surrounding tissue indicated strong graft rejection. By comparison, when using the same outbred strain of rats, allogeneic transplantation of islets within the HA-COL gel reversed long-term diabetes and prevented graft rejection in all animals. Animals were sacrificed at 40, 52, 64, and 80 weeks for evaluation, and all were non-diabetic at sacrifice. Explanted grafts revealed viable islets in the transplant site as well as intact hydrogel, with little or no evidence of fibrotic overgrowth or cellular rejection. The results of these studies demonstrate great potential for HA-COL hydrogel as an alternative to sodium alginate for long-term immunoprotected islet transplantation.

Biodegradable synthetic bone composites

DOEpatents

Liu, Gao; Zhao, Dacheng; Saiz, Eduardo; Tomsia, Antoni P.

2013-01-01

The invention provides for a biodegradable synthetic bone composition comprising a biodegradable hydrogel polymer scaffold comprising a plurality of hydrolytically unstable linkages, and an inorganic component; such as a biodegradable poly(hydroxyethylmethacrylate)/hydroxyapatite (pHEMA/HA) hydrogel composite possessing mineral content approximately that of human bone.

The effects of hyaluronic acid hydrogels with tunable mechanical properties on neural progenitor cell differentiation.

PubMed

Seidlits, Stephanie K; Khaing, Zin Z; Petersen, Rebecca R; Nickels, Jonathan D; Vanscoy, Jennifer E; Shear, Jason B; Schmidt, Christine E

2010-05-01

We report the ability to direct the differentiation pathway of neural progenitor cells (NPCs) within hydrogels having tunable mechanical properties. By modifying the polymeric sugar hyaluronic acid (HA), a major extracellular matrix component in the fetal mammalian brain, with varying numbers of photocrosslinkable methacrylate groups, hydrogels could be prepared with bulk compressive moduli spanning the threefold range measured for neonatal brain and adult spinal cord. Ventral midbrain-derived NPCs were photoencapsulated into HA hydrogels and remained viable after encapsulation. After three weeks, the majority of NPCs cultured in hydrogels with mechanical properties comparable to those of neonatal brain had differentiated into neurons (ss-III tubulin-positive), many of which had extended long, branched processes, indicative of a relatively mature phenotype. In contrast, NPCs within stiffer hydrogels, with mechanical properties comparable to those of adult brain, had differentiated into mostly astrocytes (glial fibrillary acidic protein (GFAP)-positive). Primary spinal astrocytes cultured in the hydrogel variants for two weeks acquired a spread and elongated morphology only in the stiffest hydrogels evaluated, with mechanical properties similar to adult tissue. Results demonstrate that the mechanical properties of these scaffolds can assert a defining influence on the differentiation of ventral midbrain-derived NPCs, which have strong clinical relevance because of their ability to mature into dopaminergic neurons of the substantia nigra, cells that idiopathically degenerate in individuals suffering from Parkinson's disease. Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical hydrogels based on a hyaluronic acid-graft-α-elastin derivative as potential scaffolds for tissue engineering.

PubMed

Palumbo, Fabio Salvatore; Pitarresi, Giovanna; Fiorica, Calogero; Rigogliuso, Salvatrice; Ghersi, Giulio; Giammona, Gaetano

2013-07-01

In this work hyaluronic acid (HA) functionalized with ethylenediamine (EDA) has been employed to graft α-elastin. In particular a HA-EDA derivative bearing 50 mol% of pendant amino groups has been successfully employed to produce the copolymer HA-EDA-g-α-elastin containing 32% w/w of protein. After grafting with α-elastin, remaining free amino groups reacted with ethylene glycol diglycidyl ether (EGDGE) for producing chemical hydrogels, proposed as scaffolds for tissue engineering. Swelling degree, resistance to chemical and enzymatic hydrolysis, as well as preliminary biological properties of HA-EDA-g-α-elastin/EGDGE scaffold have been evaluated and compared with a HA-EDA/EGDGE scaffold. The presence of α-elastin grafted to HA-EDA improves attachment, viability and proliferation of primary rat dermal fibroblasts and human umbilical artery smooth muscle cells. Biological performance of HA-EDA-g-α-elastin/EGDGE scaffold resulted comparable to that of a commercial collagen type I sponge (Antema®), chosen as a positive control. Copyright © 2013 Elsevier B.V. All rights reserved.

Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.

PubMed

Xiao, Bo; Xu, Zhigang; Viennois, Emilie; Zhang, Yuchen; Zhang, Zhan; Zhang, Mingzhen; Han, Moon Kwon; Kang, Yuejun; Merlin, Didier

2017-07-05

Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (∼272.3 nm) and a slightly negative zeta potential (∼-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and downregulate TNF-α, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC. Copyright © 2016 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Photo-cross-linkable methacrylated gelatin and hydroxyapatite hybrid hydrogel for modularly engineering biomimetic osteon.

PubMed

Zuo, Yicong; Liu, Xiaolu; Wei, Dan; Sun, Jing; Xiao, Wenqian; Zhao, Huan; Guo, Likun; Wei, Qingrong; Fan, Hongsong; Zhang, Xingdong

2015-05-20

Modular tissue engineering holds great potential in regenerating natural complex tissues by engineering three-dimensional modular scaffolds with predefined geometry and biological characters. In modular tissue-like construction, a scaffold with an appropriate mechanical rigidity for assembling fabrication and high biocompatibility for cell survival is the key to the successful bioconstruction. In this work, a series of composite hydrogels (GH0, GH1, GH2, and GH3) based on a combination of methacrylated gelatin (GelMA) and hydroxyapatite (HA) was exploited to enhance hydrogel mechanical rigidity and promote cell functional expression for osteon biofabrication. These composite hydrogels presented a lower swelling ratio, higher mechanical moduli, and better biocompatibility when compared to the pure GelMA hydrogel. Furthermore, on the basis of the composite hydrogel and photolithograph technology, we successfully constructed an osteon-like concentric double-ring structure in which the inner ring encapsulating human umbilical vascular endothelial cells (HUVECs) was designed to imitate blood vessel tubule while the outer ring encapsulating human osteoblast-like cells (MG63s) acts as part of bone. During the coculture period, MG63s and HUVECs exhibited not only satisfying growth status but also the enhanced genic expression of osteogenesis-related and angiogenesis-related differentiations. These results demonstrate this GelMA-HA composite hydrogel system is promising for modular tissue engineering.

Preparation, characterization and in vivo evaluation of a combination delivery system based on hyaluronic acid/jeffamine hydrogel loaded with PHBV/PLGA blend nanoparticles for prolonged delivery of Teriparatide.

PubMed

Bahari Javan, Nika; Montazeri, Hamed; Rezaie Shirmard, Leila; Jafary Omid, Nersi; Barbari, Ghullam Reza; Amini, Mohsen; Ghahremani, Mohammad Hossein; Rafiee-Tehrani, Morteza; Abedin Dorkoosh, Farid

2017-04-01

In the current study, biodegradable PHBV/PLGA blend nanoparticles (NPs) containing Teriparatide were loaded in hyaluronic acid/jeffamine (HA-JEF ED-600) hydrogel to prepare a combination delivery system (CDS) for prolonged delivery of Teriparatide. The principal purpose of the present study was to formulate an effective and prolonged Teriparatide delivery system in order to reduce the frequency of injection and thus enhance patient's compliance. Morphological properties, swelling behaviour, crosslinking efficiency and rheological characterization of HA-JEF ED-600 hydrogel were evaluated. The CDS was acquired by adding PHBV/PLGA NPs to HA-JEF ED-600 hydrogel simultaneously with crosslinking reaction. The percentage of NPs incorporation within the hydrogel as well as the loading capacity and morphology of Teriparatide loaded CDS were examined. Intrinsic fluorescence and circular dichroism spectroscopy proved that Teriparatide remains stable after processing. The release profile represented 63% Teriparatide release from CDS within 50days with lower burst release compared to NPs and hydrogel. MTT assay was conducted by using NIH3T3 cell line and no sign of reduction in cell viability was observed. Based on Miller and Tainter method, LD 50 of Teriparatide loaded CDS was 131.8mg/kg. In vivo studies demonstrated that Teriparatide loaded CDS could effectively increase serum calcium level after subcutaneous injection in mice. Favourable results in the current study introduced CDS as a promising candidate for controlled delivery of Teriparatide and pave the way for future investigations in the field of designing prolonged delivery systems for other peptides and proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Rheological Properties of Cross-Linked Hyaluronan–Gelatin Hydrogels for Tissue Engineering

PubMed Central

Vanderhooft, Janssen L.; Alcoutlabi, Mataz; Magda, Jules J.; Prestwich, Glenn D.

2009-01-01

Hydrogels that mimic the natural extracellular matrix (ECM) are used in three-dimensional cell culture, cell therapy, and tissue engineering. A semi-synthetic ECM based on cross-linked hyaluronana offers experimental control of both composition and gel stiffness. The mechanical properties of the ECM in part determine the ultimate cell phenotype. We now describe a rheological study of synthetic ECM hydrogels with storage shear moduli that span three orders of magnitude, from 11 to 3 500 Pa, a range important for engineering of soft tissues. The concentration of the chemically modified HA and the cross-linking density were the main determinants of gel stiffness. Increase in the ratio of thiol-modified gelatin reduced gel stiffness by diluting the effective concentration of the HA component. PMID:18839402

Novel self-gelling injectable hydrogel/alpha-tricalcium phosphate composites for bone regeneration: Physiochemical and microcomputer tomographical characterization.

PubMed

Douglas, Timothy E L; Schietse, Josefien; Zima, Aneta; Gorodzha, Svetlana; Parakhonskiy, Bogdan V; KhaleNkow, Dmitry; Shkarin, Roman; Ivanova, Anna; Baumbach, Tilo; Weinhardt, Venera; Stevens, Christian V; Vanhoorne, Valérie; Vervaet, Chris; Balcaen, Lieve; Vanhaecke, Frank; Slośarczyk, Anna; Surmeneva, Maria A; Surmenev, Roman A; Skirtach, Andre G

2018-03-01

Mineralized hydrogels are increasingly gaining attention as biomaterials for bone regeneration. The most common mineralization strategy has been addition of preformed inorganic particles during hydrogel formation. This maintains injectability. One common form of bone cement is formed by mixing particles of the highly reactive calcium phosphate alpha-tricalcium phosphate (α-TCP) with water to form hydroxyapatite (HA). The calcium ions released during this reaction can be exploited to crosslink anionic, calcium-binding polymers such as the polysaccharide gellan gum (GG) to induce hydrogel formation. In this study, three different amounts of α-TCP particles were added to GG polymer solution to generate novel, injectable hydrogel-inorganic composites. Distribution of the inorganic phase in the hydrogel was studied by high resolution microcomputer tomography (µCT). Gelation occurred within 30 min. α-TCP converted to HA. µCT revealed inhomogeneous distribution of the inorganic phase in the composites. These results demonstrate the potential of the composites as alternatives to traditional α-TCP bone cement and pave the way for incorporation of biologically active substances and in vitro and in vivo testing. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 822-828, 2018. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2017-08-01

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

The enhanced anti-tissue adhesive effect of injectable pluronic-HA hydrogel by poly(γ-glutamic acid).

PubMed

Kim, Manse; Hwang, Youngmin; Tae, Giyoong

2016-12-01

The stability of tissue barrier in physiological condition is a key factor to isolate the damaged site from adjacent tissue for anti-tissue adhesion. Although pluronic or pluronic-hyaluronic acid (HA) hydrogel as an injectable formulation can prevent tissue adhesion at the injection site, the anti-tissue adhesion effect is limited due to its poor stability. Herein, we prepared tissue barrier formulations composed of pluronic F127 (F127) and HA mixture (F127-HA) and the effect of the addition of poly(γ-glutamic acid) (PGA) was characterized. All of F127, HA, and F127-HA mixture showed the poor in vitro residence stability less than 3 days. However, by adding PGA into F127-HA mixture, their stability was significantly enhanced by the control of the molecular weight and concentration of PGA. Thus, F127-HA with 10wt% PGA (2000kDa) showed the long-term stability over 10 days. Similarly, the enhanced stability of F127-HA with PGA resulted in the enhanced and excellent in vivo anti-tissue adhesion effect, evidenced by histological analysis and grading of tissue adhesion. Therefore, F127-HA containing PGA could be applied as an efficient injectable tissue barrier for anti-tissue adhesion. Copyright © 2016 Elsevier B.V. All rights reserved.

Peptide Probe for Crystalline Hydroxyapatite: In Situ Detection of Biomineralization

NASA Astrophysics Data System (ADS)

Cicerone, Marcus; Becker, Matthew; Simon, Carl; Chatterjee, Kaushik

2009-03-01

While cells template mineralization in vitro and in vivo, specific detection strategies that impart chemical and structural information on this process have proven elusive. Recently we have developed an in situ based peptide probe via phage display methods that is specific to crystalline hydroxyapatite (HA). We are using this in fluorescence based assays to characterize mineralization. One application being explored is the screening of tissue engineering scaffolds for their ability to support osteogenesis. Specifically, osteoblasts are being cultured in hydrogel scaffolds possessing property gradients to provide a test bed for the HA peptide probe. Hydrogel properties that support osteogenesis and HA deposition will be identified using the probe to demonstrate its utility in optimizing design of tissue scaffolds.

Development and Translation of a Tissue-Engineered Disc in a Preclinical Rodent Model

DTIC Science & Technology

2014-12-01

annulus fibrosus tissue into full 3D Disc-like Angle Ply Structures (DAPS), inclusive of a hyaluronic acid hydrogel seeded with adult stem cells, that...AF constructs surrounding an engineered nucleus pulposus (NP) composed of a hyaluronic acid (HA) hydrogel. Measure the disc structural mechanics in...exposure to TGF-ß3 improves the functional properties of MSC-seeded photocrosslinked hyaluronic acid hydrogels by authors Minwook Kim, Isaac E

[The application of cross-linked hyaluronate hydrogel to trabeculectomy].

PubMed

Shoji, Nobuyuki; Shimizu, Kimiya; Takahashi, Katsuya; Nemoto, Rika; Kawai, Hiromi; Tomioka, Toshiya

2004-05-01

We investigated the possibility of applying cross-linked hyaluronate hydrogel (HA gel) during trabeculectomy in rabbit eyes. 1. We injected 0.9% salt solution (n = 3), Opegan-HI (n = 3), or HA gel (n = 3) into the subconjunctiva to make a follicle, and investigated its size. 2. After making a limbal-based conjunctival flap and a scleral flap, we injected HA gel or 0.9% salt solution into the subconjunctiva of rabbit eyes and sutured each flap (n = 4 each). Three weeks after the operation, we incised the conjunctiva and investigated the case of peeling away the conjunctival flap or the scleral flap. 3. We performed trabeculectomy with and without subconjunctival HA gel (n = 7 and 6, respectively), and compared the reduction of intraocular pressure between the two groups. The results showed that the formation of the follicle was excellent and it was easy to peel away the adhesion. The reduction of intraocular pressure was statistically significant 4 weeks after the operation in which the HA gel was used. It could be useful to apply HA gel in trabeculectomy to prevent adhesion.

In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation.

PubMed

Kettenberger, Ulrike; Luginbuehl, Vera; Procter, Philip; Pioletti, Dominique P

2017-07-01

Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri-implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre-osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Bone augmentation at peri-implant dehiscence defects comparing a synthetic polyethylene glycol hydrogel matrix vs. standard guided bone regeneration techniques.

PubMed

Thoma, Daniel S; Jung, Ui-Won; Park, Jin-Young; Bienz, Stefan P; Hüsler, Jürg; Jung, Ronald E

2017-07-01

The aim of the study was to test whether or not the use of a polyethylene glycol (PEG) hydrogel with or without the addition of an arginylglycylaspartic acid (RGD) sequence applied as a matrix in combination with hydroxyapatite/tricalciumphosphate (HA/TCP) results in similar peri-implant bone regeneration as traditional guided bone regeneration procedures. In 12 beagle dogs, implant placement and peri-implant bone regeneration were performed 2 months after tooth extraction in the maxilla. Two standardized box-shaped defects were bilaterally created, and dental implants were placed in the center of the defects with a dehiscence of 4 mm. Four treatment modalities were randomly applied: i)HA/TCP mixed with a synthetic PEG hydrogel, ii)HA/TCP mixed with a synthetic PEG hydrogel supplemented with an RGD sequence, iii)HA/TCP covered with a native collagen membrane (CM), iv)and no bone augmentation (empty). After a healing period of 8 or 16 weeks, micro-CT and histological analyses were performed. Histomorphometric analysis revealed a greater relative augmented area for groups with bone augmentation (43.3%-53.9% at 8 weeks, 31.2%-42.8% at 16 weeks) compared to empty controls (22.9% at 8 weeks, 1.1% at 16 weeks). The median amount of newly formed bone was greatest in group CM at both time-points. Regarding the first bone-to-implant contact, CM was statistically significantly superior to all other groups at 8 weeks. Bone can partially be regenerated at peri-implant buccal dehiscence defects using traditional guided bone regeneration techniques. The use of a PEG hydrogel applied as a matrix mixed with a synthetic bone substitute material might lack a sufficient stability over time for this kind of defect. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Poly(vinyl alcohol) hydrogel coatings with tunable surface exposure of hydroxyapatite

PubMed Central

Moreau, David; Villain, Arthur; Ku, David N; Corté, Laurent

2014-01-01

Insufficient bone anchoring is a major limitation of artificial substitutes for connective osteoarticular tissues. The use of coatings containing osseoconductive ceramic particles is one of the actively explored strategies to improve osseointegration and strengthen the bone-implant interface for general tissue engineering. Our hypothesis is that hydroxyapatite (HA) particles can be coated robustly on specific assemblies of PVA hydrogel fibers for the potential anchoring of ligament replacements. A simple dip-coating method is described to produce composite coatings made of microscopic hydroxyapatite (HA) particles dispersed in a poly(vinyl alcohol) (PVA) matrix. The materials are compatible with the requirements for implant Good Manufacturing Practices. They are applied to coat bundles of PVA hydrogel fibers used for the development of ligament implants. By means of optical and electronic microscopy, we show that the coating thickness and surface state can be adjusted by varying the composition of the dipping solution. Quantitative analysis based on backscattered electron microscopy show that the exposure of HA at the coating surface can be tuned from 0 to over 55% by decreasing the weight ratio of PVA over HA from 0.4 to 0.1. Abrasion experiments simulating bone-implant contact illustrate how the coating cohesion and wear resistance increase by increasing the content of PVA relative to HA. Using pullout experiments, we find that these coatings adhere well to the fiber bundles and detach by propagation of a crack inside the coating. These results provide a guide to select coated implants for anchoring artificial ligaments. PMID:25482413

Tunable hydrogel composite with two-step processing in combination with innovative hardware upgrade for cell-based three-dimensional bioprinting.

PubMed

Wüst, Silke; Godla, Marie E; Müller, Ralph; Hofmann, Sandra

2014-02-01

Three-dimensional (3-D) bioprinting is the layer-by-layer deposition of biological material with the aim of achieving stable 3-D constructs for application in tissue engineering. It is a powerful tool for the spatially directed placement of multiple materials and/or cells within the 3-D sample. Encapsulated cells are protected by the bioink during the printing process. Very few materials are available that fulfill requirements for bioprinting as well as provide adequate properties for cell encapsulation during and after the printing process. A hydrogel composite including alginate and gelatin precursors was tuned with different concentrations of hydroxyapatite (HA) and characterized in terms of rheology, swelling behavior and mechanical properties to assess the versatility of the system. Instantaneous as well as long-term structural integrity of the printed hydrogel was achieved with a two-step mechanism combining the thermosensitive properties of gelatin with chemical crosslinking of alginate. Novel syringe tip heaters were developed for improved temperature control of the bioink to avoid clogging. Human mesenchymal stem cells mixed into the hydrogel precursor survived the printing process and showed high cell viability of 85% living cells after 3 days of subsequent in vitro culture. HA enabled the visualization of the printed structures with micro-computed tomography. The inclusion of HA also favors the use of the bioink for bone tissue engineering applications. By adding factors other than HA, the composite could be used as a bioink for applications in drug delivery, microsphere deposition or soft tissue engineering. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Property-based design: optimization and characterization of polyvinyl alcohol (PVA) hydrogel and PVA-matrix composite for artificial cornea.

PubMed

Jiang, Hong; Zuo, Yi; Zhang, Li; Li, Jidong; Zhang, Aiming; Li, Yubao; Yang, Xiaochao

2014-03-01

Each approach for artificial cornea design is toward the same goal: to develop a material that best mimics the important properties of natural cornea. Accordingly, the selection and optimization of corneal substitute should be based on their physicochemical properties. In this study, three types of polyvinyl alcohol (PVA) hydrogels with different polymerization degree (PVA1799, PVA2499 and PVA2699) were prepared by freeze-thawing techniques. After characterization in terms of transparency, water content, water contact angle, mechanical property, root-mean-square roughness and protein adsorption behavior, the optimized PVA2499 hydrogel with similar properties of natural cornea was selected as a matrix material for artificial cornea. Based on this, a biomimetic artificial cornea was fabricated with core-and-skirt structure: a transparent PVA hydrogel core, surrounding by a ringed PVA-matrix composite skirt that composed of graphite, Fe-doped nano hydroxyapatite (n-Fe-HA) and PVA hydrogel. Different ratio of graphite/n-Fe-HA can tune the skirt color from dark brown to light brown, which well simulates the iris color of Oriental eyes. Moreover, morphologic and mechanical examination showed that an integrated core-and-skirt artificial cornea was formed from an interpenetrating polymer network, no phase separation appeared on the interface between the core and the skirt.

Injectable hydrogels for treatment of osteoarthritis - A rheological study.

PubMed

von Lospichl, Benjamin; Hemmati-Sadeghi, Shabnam; Dey, Pradip; Dehne, Tilo; Haag, Rainer; Sittinger, Michael; Ringe, Jochen; Gradzielski, Michael

2017-11-01

Osteoarthritis (OA) is a disabling condition especially in the elderly population. The current therapeutic approaches do not halt the OA progression or reverse joint damage. In order to overcome the problem of rapid clearance of hyaluronic acid (HA), a standard viscosupplement for OA, we investigated the rheological properties of a relatively non-degradable dendritic polyglycerol sulfate (dPGS) hydrogel to determine a suitable concentration for intra articular injections that mimics HA in terms of its viscoelastic and mechanical properties. To do so, the concentration range from 3.6 to 4.8wt% of dPGS and, as a reference, blends of commercially available HAs (Ostenil ® , GO-ON ® , Synocrom ® Forte and Synvisc ® ), were investigated by means of oscillating and flow rheology, thereby yielding storage (G') and loss modulus (G"), as well as yield stress and shear viscosity. In our rheological experiments we observe a pronounced coupling of the molecular weight and the rheological properties for the HAs. Furthermore, we find the dPGS hydrogel to form more compact networks with increasing concentration. From a broader comparison the current findings suggest that an overall polymer concentration of 4.0wt% dPGS has viscoelastic properties that are comparable to hyaluronic acid in the medically relevant frequency range, where for medical application the dPGS hydrogel has the advantage of being much less easily displaced from its injection place than HA. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2018-04-01

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

Efforts to eradicate yellow crazy ants on Johnston Atoll: Results from Crazy Ant Strike Team IX, December 2014-June 2015

USGS Publications Warehouse

Banko, Paul C.; Peck, Robert W.; Donmoyer, Kevin; Kropidlowski, Stephan; Pollock, Amanda

2015-01-01

The ecologically destructive yellow crazy ant (YCA; Anoplolepis gracilipes) was first detected on Johnston Atoll in January 2010. Within eight months, the U.S. Fish and Wildlife Service had mobilized its first crazy ant strike team (CAST), a group of biologists dedicated to testing and identifying insecticidal baits to be used to eradicate the ant on the atoll. During December 2014‒May 2015 CAST IX focused on testing hydrogel crystals saturated with sucrose solution (25%) carrying the insecticides thiamethoxam and dinotefuran against YCA. A series of experiments, including artificial nest box trials, and field-based palatability trials and eradication tests on small (500 m2 or 0.05 ha) and large plots (2500 m2 or 0.25 ha), were conducted to test concentrations of thiamethoxam ranging from 0.0005% to 0.01%, and dinotefuran at 0.05%. Additionally, the cat food-based matrix containing dinotefuran (0.05%), the standard bait used to suppress YCA on Johnston since 2011, and textured vegetable protein (TVP) carrying dinotefuran at 0.1% and 0.05% were included in large plot tests. Nest box trials were inconclusive due to a consistent loss of queen and worker ants in control boxes, so they were discontinued. Palatability trials suggested higher dosages of thiamethoxam (0.005 and 0.01%) were less attractive than lower dosages (0.0005 and 0.001%) and controls (sucrose only), but small and large plot experiments failed to identify a thiamethoxam concentration that was consistently effective at killing YCA. In contrast, hydrogel containing dinotefuran was consistently effective, killing >95% of YCA on small and large plots. As expected, the cat food bait effectively reduced YCA abundances, but was slightly less effective than hydrogel containing dinotefuran over time. Three successive, approximately weekly treatments of large plots with hydrogel bait, or other baits followed by hydrogel bait, suggest an increasing overall effectiveness, with no aversion of YCA to the bait. This finding is important in that it indicates that hydrogel bait can be applied at short time intervals, potentially resulting in relatively constant exposure of YCA to highly attractive, yet toxic, sucrose-based bait. TVP performed similar to hydrogel, reducing YCA abundance >92% at both concentrations tested. Finally, dosages of hydrogel containing dinotefuran at 6, 12 and 24 l/0.25 ha were all effective at reducing YCA on large plots. Overall, results from these experiments suggest that hydrogel containing dinotefuran (0.05%) is a promising tool for eradicating YCA on Johnston Atoll.

Engineered Joint Lubrication for OA Prevention and Treatment

DTIC Science & Technology

2015-09-01

Williams, C. G., Khan, M., Manson, P. & Elisseeff, J .H. In vivo chondrogenesis of mesenchymal stem cells in photopolymerized hydrogel. Plast...protecting cells from free-radical damage20–22. Coating surfaces with HA may also physically protect the surfaces from cytokines and degrading enzymes...modification provides a biomimetic mechanism to concentrate HA on the surface. Numerous endogenous enzymes and reactive oxygen species can degrade HA

Anatomic Mesenchymal Stem Cell-Based Engineered Cartilage Constructs for Biologic Total Joint Replacement

PubMed Central

Saxena, Vishal; Kim, Minwook; Keah, Niobra M.; Neuwirth, Alexander L.; Stoeckl, Brendan D.; Bickard, Kevin; Restle, David J.; Salowe, Rebecca; Wang, Margaret Ye; Steinberg, David R.

2016-01-01

Cartilage has a poor healing response, and few viable options exist for repair of extensive damage. Hyaluronic acid (HA) hydrogels seeded with mesenchymal stem cells (MSCs) polymerized through UV crosslinking can generate functional tissue, but this crosslinking is not compatible with indirect rapid prototyping utilizing opaque anatomic molds. Methacrylate-modified polymers can also be chemically crosslinked in a cytocompatible manner using ammonium persulfate (APS) and N,N,N′,N′-tetramethylethylenediamine (TEMED). The objectives of this study were to (1) compare APS/TEMED crosslinking with UV crosslinking in terms of functional maturation of MSC-seeded HA hydrogels; (2) generate an anatomic mold of a complex joint surface through rapid prototyping; and (3) grow anatomic MSC-seeded HA hydrogel constructs using this alternative crosslinking method. Juvenile bovine MSCs were suspended in methacrylated HA (MeHA) and crosslinked either through UV polymerization or chemically with APS/TEMED to generate cylindrical constructs. Minipig porcine femoral heads were imaged using microCT, and anatomic negative molds were generated by three-dimensional printing using fused deposition modeling. Molded HA constructs were produced using the APS/TEMED method. All constructs were cultured for up to 12 weeks in a chemically defined medium supplemented with TGF-β3 and characterized by mechanical testing, biochemical assays, and histologic analysis. Both UV- and APS/TEMED-polymerized constructs showed increasing mechanical properties and robust proteoglycan and collagen deposition over time. At 12 weeks, APS/TEMED-polymerized constructs had higher equilibrium and dynamic moduli than UV-polymerized constructs, with no differences in proteoglycan or collagen content. Molded HA constructs retained their hemispherical shape in culture and demonstrated increasing mechanical properties and proteoglycan and collagen deposition, especially at the edges compared to the center of these larger constructs. Immunohistochemistry showed abundant collagen type II staining and little collagen type I staining. APS/TEMED crosslinking can be used to produce MSC-seeded HA-based neocartilage and can be used in combination with rapid prototyping techniques to generate anatomic MSC-seeded HA constructs for use in filling large and anatomically complex chondral defects or for biologic joint replacement. PMID:26871863

Cartilage Repair Using Composites of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel in a Minipig Model.

PubMed

Ha, Chul-Won; Park, Yong-Beom; Chung, Jun-Young; Park, Yong-Geun

2015-09-01

The cartilage regeneration potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with a hyaluronic acid (HA) hydrogel composite has shown remarkable results in rat and rabbit models. The purpose of the present study was to confirm the consistent regenerative potential in a pig model using three different cell lines. A full-thickness chondral injury was intentionally created in the trochlear groove of each knee in 6 minipigs. Three weeks later, an osteochondral defect, 5 mm wide by 10 mm deep, was created, followed by an 8-mm-wide and 5-mm-deep reaming. A mixture (1.5 ml) of hUCB-MSCs (0.5×10(7) cells per milliliter) and 4% HA hydrogel composite was then transplanted into the defect on the right knee. Each cell line was used in two minipigs. The osteochondral defect created in the same manner on the left knee was untreated to act as the control. At 12 weeks postoperatively, the pigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. The cellular characteristics (e.g., cellular proliferation and chondrogenic differentiation capacity) of the hUCB-MSCs influenced the degree of cartilage regeneration potential. This evidence of consistent cartilage regeneration using composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future. To date, several studies have investigated the chondrogenic potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs); however, the preclinical studies are still limited in numbers with various results. In parallel, in the past several years, the cartilage regeneration potential of hUCB-MSCs with a hyaluronic acid (HA) hydrogel composite have been investigated and remarkable results in rat and rabbit models have been attained. (These experimental results are currently in preparation for publication.) Before applying the cartilage regeneration technique in a human clinical trial, it seemed necessary to confirm the consistent result in a larger animal model. At 12 weeks postoperatively, the minipigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. This evidence of consistent cartilage regeneration with composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future. ©AlphaMed Press.

Cartilage Repair Using Composites of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel in a Minipig Model

PubMed Central

Ha, Chul-Won; Chung, Jun-Young; Park, Yong-Geun

2015-01-01

The cartilage regeneration potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with a hyaluronic acid (HA) hydrogel composite has shown remarkable results in rat and rabbit models. The purpose of the present study was to confirm the consistent regenerative potential in a pig model using three different cell lines. A full-thickness chondral injury was intentionally created in the trochlear groove of each knee in 6 minipigs. Three weeks later, an osteochondral defect, 5 mm wide by 10 mm deep, was created, followed by an 8-mm-wide and 5-mm-deep reaming. A mixture (1.5 ml) of hUCB-MSCs (0.5 × 107 cells per milliliter) and 4% HA hydrogel composite was then transplanted into the defect on the right knee. Each cell line was used in two minipigs. The osteochondral defect created in the same manner on the left knee was untreated to act as the control. At 12 weeks postoperatively, the pigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. The cellular characteristics (e.g., cellular proliferation and chondrogenic differentiation capacity) of the hUCB-MSCs influenced the degree of cartilage regeneration potential. This evidence of consistent cartilage regeneration using composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future. Significance To date, several studies have investigated the chondrogenic potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs); however, the preclinical studies are still limited in numbers with various results. In parallel, in the past several years, the cartilage regeneration potential of hUCB-MSCs with a hyaluronic acid (HA) hydrogel composite have been investigated and remarkable results in rat and rabbit models have been attained. (These experimental results are currently in preparation for publication.) Before applying the cartilage regeneration technique in a human clinical trial, it seemed necessary to confirm the consistent result in a larger animal model. At 12 weeks postoperatively, the minipigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. This evidence of consistent cartilage regeneration with composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future. PMID:26240434

Fabrication of Novel Hydrogel with Berberine-Enriched Carboxymethylcellulose and Hyaluronic Acid as an Anti-Inflammatory Barrier Membrane

PubMed Central

Huang, Yu-Chih; Huang, Kuen-Yu; Yang, Bing-Yuan

2016-01-01

An antiadhesion barrier membrane is an important biomaterial for protecting tissue from postsurgical complications. However, there is room to improve these membranes. Recently, carboxymethylcellulose (CMC) incorporated with hyaluronic acid (HA) as an antiadhesion barrier membrane and drug delivery system has been reported to provide excellent tissue regeneration and biocompatibility. The aim of this study was to fabricate a novel hydrogel membrane composed of berberine-enriched CMC prepared from bark of the P. amurense tree and HA (PE-CMC/HA). In vitro anti-inflammatory properties were evaluated to determine possible clinical applications. The PE-CMC/HA membranes were fabricated by mixing PE-CMC and HA as a base with the addition of polyvinyl alcohol to form a film. Tensile strength and ultramorphology of the membrane were evaluated using a universal testing machine and scanning electron microscope, respectively. Berberine content of the membrane was confirmed using a UV-Vis spectrophotometer at a wavelength of 260 nm. Anti-inflammatory property of the membrane was measured using a Griess reaction assay. Our results showed that fabricated PE-CMC/HA releases berberine at a concentration of 660 μg/ml while optimal plasticity was obtained at a 30 : 70 PE-CMC/HA ratio. The berberine-enriched PE-CMC/HA had an inhibited 60% of inflammation stimulated by LPS. These results suggest that the PE-CMC/HA membrane fabricated in this study is a useful anti-inflammatory berberine release system. PMID:28119926

Hyaluronic Acid and Its Derivatives in Coating and Delivery Systems: Applications in Tissue Engineering, Regenerative Medicine and Immunomodulation.

PubMed

Knopf-Marques, Helena; Pravda, Martin; Wolfova, Lucie; Velebny, Vladimir; Schaaf, Pierre; Vrana, Nihal Engin; Lavalle, Philippe

2016-11-01

As an Extracellular Matrix (ECM) component, Hyaluronic acid (HA) plays a multi-faceted role in cell migration, proliferation and differentiation at micro level and system level events such as tissue water homeostasis. Among its biological functions, it is known to interact with cytokines and contribute to their retention in ECM microenvironment. In addition to its biological functions, it has advantageous physical properties which result in the industrial endeavors in the synthesis and extraction of HA for variety of applications ranging from medical to cosmetic. Recently, HA and its derivatives have been the focus of active research for applications in biomedical device coatings, drug delivery systems and in the form of scaffolds or cell-laden hydrogels for tissue engineering. A specific reason for the increase in use of HA based structures is their immunomodulatory and regeneration inducing capacities. In this context, this article reviews recent literature on modulation of the implantable biomaterial microenvironment by systems based on HA and its derivatives, particularly hydrogels and microscale coatings that are able to deliver cytokines in order to reduce the adverse immune reactions and promote tissue healing. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An In Vivo Study of Composite Microgels Based on Hyaluronic Acid and Gelatin for the Reconstruction of Surgically Injured Rat Vocal Folds

PubMed Central

Coppoolse, Jiska M. S.; Van Kooten, T. G.; Heris, Hossein K.; Mongeau, Luc; Li, Nicole Y. K.; Thibeault, Susan L.; Pitaro, Jacob; Akinpelu, Olubunmi; Daniel, Sam J.

2016-01-01

Purpose The objective of this study was to investigate local injection with a hierarchically microstructured hyaluronic acid–gelatin (HA-Ge) hydrogel for the treatment of acute vocal fold injury using a rat model. Method Vocal fold stripping was performed unilaterally in 108 Sprague-Dawley rats. A volume of 25 ml saline (placebo controls), HA-bulk, or HA-Ge hydrogel was injected into the lamina propria (LP) 5 days after surgery. The vocal folds were harvested at 3, 14, and 28 days after injection and analyzed using hematoxylin and eosin staining and immunohistochemistry staining for macrophages, myofibroblasts, elastin, collagen type I, and collagen type III. Results The macrophage count was statistically significantly lower in the HA-Ge group than in the saline group (p < .05) at Day 28. Results suggested that the HA-Ge injection did not induce inflammatory or rejection response. Myofibroblast counts and elastin were statistically insignificant across treatment groups at all time points. Increased elastin deposition was qualitatively observed in both HA groups from Day 3 to Day 28, and not in the saline group. Significantly more elastin was observed in the HA-bulk group than in the uninjured group at Day 28. Significantly more collagen type I was observed in the HA-bulk and HA-Ge groups than in the saline group (p < .05) at Day 28. The collagen type I concentration in the HA-Ge and saline groups was found to be comparable to that in the uninjured controls at Day 28. The concentration of collagen type III in all treatment groups was similar to that in uninjured controls at Day 28. Conclusion Local HA-Ge and HA-bulk injections for acute injured vocal folds were biocompatible and did not induce adverse response. PMID:24687141

A novel thermo-sensitive hydrogel based on thiolated chitosan/hydroxyapatite/beta-glycerophosphate.

PubMed

Liu, Xujie; Chen, Yan; Huang, Qianli; He, Wei; Feng, Qingling; Yu, Bo

2014-09-22

In order to get a water-soluble in situ gel-forming system, a thiolated chitosan, chitosan-4-thio-butylamidine (CS-TBA) conjugate was synthesized and used to replace the unmodified chitosan in the application of the in situ gel-forming system. A novel thermo-sensitive hydrogel was prepared based on CS-TBA/hydroxyapatite (HA)/beta-glycerophosphate disodium (β-GP). The gel formation, rheological properties, morphology, degradation, cytotoxicity, as well as protein release process of the novel gel system were investigated in this study. The CS-TBA/HA/β-GP gel showed a higher storage modulus (G') and loss modulus (G″) and a decreased bovine serum albumin (BSA) release rate which was maintained the protein release for a longer time compared with the unmodified chitosan (CS)/HA/β-GP gel, due to the existence of thiol groups and/or disulfide bonds. The CS-TBA/HA/β-GP gel has a porous structure with a uniform distribution of nano-hydroxyapatite, an appropriate degradation rate and low cytotoxicity, showing potential applications in drug delivery and tissue engineering. Copyright © 2014 Elsevier Ltd. All rights reserved.

3D culture of human pluripotent stem cells in RGD-alginate hydrogel improves retinal tissue development.

PubMed

Hunt, Nicola C; Hallam, Dean; Karimi, Ayesha; Mellough, Carla B; Chen, Jinju; Steel, David H W; Lako, Majlinda

2017-02-01

No treatments exist to effectively treat many retinal diseases. Retinal pigmented epithelium (RPE) and neural retina can be generated from human embryonic stem cells/induced pluripotent stem cells (hESCs/hiPSCs). The efficacy of current protocols is, however, limited. It was hypothesised that generation of laminated neural retina and/or RPE from hiPSCs/hESCs could be enhanced by three dimensional (3D) culture in hydrogels. hiPSC- and hESC-derived embryoid bodies (EBs) were encapsulated in 0.5% RGD-alginate; 1% RGD-alginate; hyaluronic acid (HA) or HA/gelatin hydrogels and maintained until day 45. Compared with controls (no gel), 0.5% RGD-alginate increased: the percentage of EBs with pigmented RPE foci; the percentage EBs with optic vesicles (OVs) and pigmented RPE simultaneously; the area covered by RPE; frequency of RPE cells (CRALBP+); expression of RPE markers (TYR and RPE65) and the retinal ganglion cell marker, MATH5. Furthermore, 0.5% RGD-alginate hydrogel encapsulation did not adversely affect the expression of other neural retina markers (PROX1, CRX, RCVRN, AP2α or VSX2) as determined by qRT-PCR, or the percentage of VSX2 positive cells as determined by flow cytometry. 1% RGD-alginate increased the percentage of EBs with OVs and/or RPE, but did not significantly influence any other measures of retinal differentiation. HA-based hydrogels had no significant effect on retinal tissue development. The results indicated that derivation of retinal tissue from hESCs/hiPSCs can be enhanced by culture in 0.5% RGD-alginate hydrogel. This RGD-alginate scaffold may be useful for derivation, transport and transplantation of neural retina and RPE, and may also enhance formation of other pigmented, neural or epithelial tissue. The burden of retinal disease is ever growing with the increasing age of the world-wide population. Transplantation of retinal tissue derived from human pluripotent stem cells (PSCs) is considered a promising treatment. However, derivation of retinal tissue from PSCs using defined media is a lengthy process and often variable between different cell lines. This study indicated that alginate hydrogels enhanced retinal tissue development from PSCs, whereas hyaluronic acid-based hydrogels did not. This is the first study to show that 3D culture with a biomaterial scaffold can improve retinal tissue derivation from PSCs. These findings indicate potential for the clinical application of alginate hydrogels for the derivation and subsequent transplantation retinal tissue. This work may also have implications for the derivation of other pigmented, neural or epithelial tissue. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model

PubMed Central

Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li; Wu, Qinjie; Gong, Changyang

2016-01-01

Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate. PMID:27869192

Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model

NASA Astrophysics Data System (ADS)

Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li; Wu, Qinjie; Gong, Changyang

2016-11-01

Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate.

Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells.

PubMed

Duan, B; Kapetanovic, E; Hockaday, L A; Butcher, J T

2014-05-01

Tissue engineering has great potential to provide a functional de novo living valve replacement, capable of integration with host tissue and growth. Among various valve conduit fabrication techniques, three-dimensional (3-D) bioprinting enables deposition of cells and hydrogels into 3-D constructs with anatomical geometry and heterogeneous mechanical properties. Successful translation of this approach, however, is constrained by the dearth of printable and biocompatible hydrogel materials. Furthermore, it is not known how human valve cells respond to these printed environments. In this study, 3-D printable formulations of hybrid hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC). Increasing Me-Gel concentration resulted in lower stiffness and higher viscosity, facilitated cell spreading, and better maintained HAVIC fibroblastic phenotype. Bioprinting accuracy was dependent upon the relative concentrations of Me-Gel and Me-HA, but when optimized enabled the fabrication of a trileaflet valve shape accurate to the original design. HAVIC encapsulated within bioprinted heart valves maintained high viability, and remodeled the initial matrix by depositing collagen and glyosaminoglycans. These findings represent the first rational design of bioprinted trileaflet valve hydrogels that regulate encapsulated human VIC behavior. The use of anatomically accurate living valve scaffolds through bioprinting may accelerate understanding of physiological valve cell interactions and progress towards de novo living valve replacements. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Directing three-dimensional multicellular morphogenesis by self-organization of vascular mesenchymal cells in hyaluronic acid hydrogels.

PubMed

Zhu, Xiaolu; Gojgini, Shiva; Chen, Ting-Hsuan; Fei, Peng; Dong, Siyan; Ho, Chih-Ming; Segura, Tatiana

2017-01-01

Physical scaffolds are useful for supporting cells to form three-dimensional (3D) tissue. However, it is non-trivial to develop a scheme that can robustly guide cells to self-organize into a tissue with the desired 3D spatial structures. To achieve this goal, the rational regulation of cellular self-organization in 3D extracellular matrix (ECM) such as hydrogel is needed. In this study, we integrated the Turing reaction-diffusion mechanism with the self-organization process of cells and produced multicellular 3D structures with the desired configurations in a rational manner. By optimizing the components of the hydrogel and applying exogenous morphogens, a variety of multicellular 3D architectures composed of multipotent vascular mesenchymal cells (VMCs) were formed inside hyaluronic acid (HA) hydrogels. These 3D architectures could mimic the features of trabecular bones and multicellular nodules. Based on the Turing reaction-diffusion instability of morphogens and cells, a theoretical model was proposed to predict the variations observed in 3D multicellular structures in response to exogenous factors. It enabled the feasibility to obtain diverse types of 3D multicellular structures by addition of Noggin and/or BMP2. The morphological consistency between the simulation prediction and experimental results probably revealed a Turing-type mechanism underlying the 3D self-organization of VMCs in HA hydrogels. Our study has provided new ways to create a variety of self-organized 3D multicellular architectures for regenerating biomaterial and tissues in a Turing mechanism-based approach.

Hyaluronic Acid (HA)-Polyethylene glycol (PEG) as injectable hydrogel for intervertebral disc degeneration patients therapy

NASA Astrophysics Data System (ADS)

Putri Kwarta, Cityta; Widiyanti, Prihartini; Siswanto

2017-05-01

Chronic Low Back Pain (CLBP) is one health problem that is often encountered in a community. Inject-able hydrogels are the newest way to restore the disc thickness and hydration caused by disc degeneration by means of minimally invasive surgery. Thus, polymers can be combined to improve the characteristic properties of inject-able hydrogels, leading to use of Hyaluronic Acid (a natural polymer) and Polyethylene glycol (PEG) with Horse Radish Peroxide (HRP) cross linker enzymes. The swelling test results, which approaches were the ideal disc values, were sampled with variation of enzyme concentrations of 0.25 µmol/min/mL. The enzyme concentrations were 33.95%. The degradation test proved that the sample degradation increased along with the decrease of the HRP enzyme concentration. The results of the cytotoxicity assay with MTT assay method showed that all samples resulted in the 90% of living cells are not toxic. In vitro injection, models demonstrated that higher concentration of the enzymes was less state of gel which would rupture when released from the agarose gel. The functional group characterization shows the cross linking bonding in sample with enzyme adding. The conclusion of this study is PEG-HA-HRP enzyme are safe polymer composites which have a potential to be applied as an injectable hydrogel for intervertebral disc degeneration.

Incorporation of Active DNA/Cationic Polymer Polyplexes into Hydrogel Scaffolds

PubMed Central

Lei, Yuguo; Huang, Suxian; Sharif-Kashani, Pooria; Chen, Yong; Kavehpour, Pirouz; Segura, Tatiana

2010-01-01

The effective and sustained delivery of DNA and siRNAs locally would increase the applicability of gene therapy in tissue regeneration and cancer therapy. One promising approach is to use hydrogel scaffolds to encapsulate and deliver nucleotides in the form of nanoparticles to the disease sites. However, this approach is currently limited by the inability to load concentrated and active gene delivery nanoparticles into the hydrogels due to the severe nanoparticle aggregation during the loading process. Here, we present a process to load concentrated and un-aggregated non-viral gene delivery nanoparticles, using DNA/polyethylene imine (PEI) polyplexes as an example, into neutral polyethylene glycol (PEG), negatively charged hyaluronic acid (HA) and protein fibrin hydrogels crosslinked through various chemistries. The encapsulated polyplexes are highly active both in vitro and in vivo. We believe this process will significantly advance the applications of hydrogel scaffold mediated non-viral gene delivery in tissue regeneration and cancer therapy. PMID:20822811

Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine

PubMed Central

Nguyen, Minh Khanh; Alsberg, Eben

2014-01-01

Polymer hydrogels have been widely explored as therapeutic delivery matrices because of their ability to present sustained, localized and controlled release of bioactive factors. Bioactive factor delivery from injectable biopolymer hydrogels provides a versatile approach to treat a wide variety of diseases, to direct cell function and to enhance tissue regeneration. The innovative development and modification of both natural-(e.g., alginate (ALG), chitosan, hyaluronic acid (HA), gelatin, heparin (HEP), etc.) and synthetic-(e.g., polyesters, polyethyleneimine (PEI), etc.) based polymers has resulted in a variety of approaches to design drug delivery hydrogel systems from which loaded therapeutics are released. This review presents the state-of-the-art in a wide range of hydrogels that are formed though self-assembly of polymers and peptides, chemical crosslinking, ionic crosslinking and biomolecule recognition. Hydrogel design for bioactive factor delivery is the focus of the first section. The second section then thoroughly discusses release strategies of payloads from hydrogels for therapeutic medicine, such as physical incorporation, covalent tethering, affinity interactions, on demand release and/or use of hybrid polymer scaffolds, with an emphasis on the last 5 years. PMID:25242831

Effects of Hydrogel Stiffness and Extracellular Compositions on Modulating Cartilage Regeneration by Mixed Populations of Stem Cells and Chondrocytes In Vivo.

PubMed

Wang, Tianyi; Lai, Janice H; Yang, Fan

2016-12-01

Cell-based therapies offer great promise for repairing cartilage. Previous strategies often involved using a single cell population such as stem cells or chondrocytes. A mixed cell population may offer an alternative strategy for cartilage regeneration while overcoming donor scarcity. We have recently reported that adipose-derived stem cells (ADSCs) can catalyze neocartilage formation by neonatal chondrocytes (NChons) when mixed co-cultured in 3D hydrogels in vitro. However, it remains unknown how the biochemical and mechanical cues of hydrogels modulate cartilage formation by mixed cell populations in vivo. The present study seeks to answer this question by co-encapsulating ADSCs and NChons in 3D hydrogels with tunable stiffness (∼1-33 kPa) and biochemical cues, and evaluating cartilage formation in vivo using a mouse subcutaneous model. Three extracellular matrix molecules were examined, including chondroitin sulfate (CS), hyaluronic acid (HA), and heparan sulfate (HS). Our results showed that the type of biochemical cue played a dominant role in modulating neocartilage deposition. CS and HA enhanced type II collagen deposition, a desirable phenotype for articular cartilage. In contrast, HS promoted fibrocartilage phenotype with the upregulation of type I collagen and failed to retain newly deposited matrix. Hydrogels with stiffnesses of ∼7-33 kPa led to a comparable degree of neocartilage formation, and a minimal initial stiffness was required to retain hydrogel integrity over time. Results from this study highlight the important role of matrix cues in directing neocartilage formation, and they offer valuable insights in guiding optimal scaffold design for cartilage regeneration by using mixed cell populations.

In vivo engineering of the vocal fold extracellular matrix with injectable hyaluronic acid hydrogels: early effects on tissue repair and biomechanics in a rabbit model.

PubMed

Hansen, Jennifer K; Thibeault, Susan L; Walsh, Jennifer F; Shu, Xiao Zheng; Prestwich, Glenn D

2005-09-01

A prospective, controlled animal study was performed to determine whether the use of injectable, chemically modified hyaluronic acid (HA) derivatives at the time of intentional vocal fold resection might facilitate wound repair and preserve the unique viscoelastic properties of the vocal fold extracellular matrix. We performed bilateral vocal fold biopsies on 33 rabbits. Two groups of rabbits were unilaterally treated with 2 different HA derivatives--Carbylan-SX and HA-DTPH-PEGDA--at the time of resection. Saline was injected as a control into the contralateral fold. The animals were painlessly sacrificed 3 weeks after biopsy and injection. The outcomes measured included histologic fibrosis level, tissue HA level, and tissue viscosity and elasticity. The Carbylan-SX-treated vocal folds were found to have significantly less fibrosis than the saline-treated controls. The levels of HA in the treated vocal folds were not significantly different from those in the controls at 3 weeks as measured by enzyme-linked immunosorbent assay. The Carbylan-SX-treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. The HA-DTPH-PEGDA injections yielded significantly improved viscosity, but not elasticity. Prophylactic in vivo manipulation of the extracellular matrix with an injectable Carbylan-SX hydrogel appears to induce vocal fold tissue regeneration to yield optimal tissue composition and biomechanical properties favorable for phonation.

In Vivo engineering of the vocal fold ECM with injectable HA hydrogels-late effects on tissue repair and biomechanics in a rabbit model.

PubMed

Thibeault, Susan L; Klemuk, Sarah A; Chen, Xia; Quinchia Johnson, Beatriz H

2011-03-01

To determine if the utilization of injectable chemically modified hyaluronan (HA) derivative at the time of intentional vocal fold resection may facilitate wound repair and preserve the unique viscoelastic properties of the extracellular matrix (ECM) and lamina propria 6 months after treatment. Prospective, controlled animal study. Twelve rabbit vocal folds were biopsied bilaterally, and the left side of vocal fold was treated with Extracel, an injectable, chemically modified HA derivative, and the right side of vocal fold was injected with saline as control at the time of resection. Animals were sacrificed 6 months after biopsy and injection. Outcomes measured include transcription levels for procollagen, fibronectin, fibromodulin, transforming growth factor beta one (TGF-β1), HA synthase, and hyaluronidase, and tissue biomechanics-viscosity and elasticity. Extracel-treated vocal folds were found to have significantly less fibrosis than saline-treated controls. Extracel-treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. Significantly decreased levels of fibronectin, fibromodulin, TGF-β1, procollagen I, and HA synthase were measured. Prophylactic in vivo manipulation of the ECM with an injectable HA hydrogel appears to induce vocal fold tissue regeneration to yield improved tissue composition and biomechanical properties at 6 months. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices.

PubMed

Zhang, J; Wang, Q; Wang, A

2010-02-01

In order to find a new way to slow down the release of drugs and to solve the burst release problem of drugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium alginate/hydroxyapatite (SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in the beads during the sol-gel transition process of SA. The SA/HA nanocomposites were characterized by Fourier transform IR spectroscopy, X-ray fluorescence spectrometry, scanning electron microscopy and field emission SEM in order to reveal their composition and surface morphology as well as the role that the in situ generated HA micro-particles play. The factors influencing the swelling behavior, drug loading and controlled release behavior of the SA/HA nanocomposite beads were also investigated using diclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the nanocomposites, which could contract and restrict the movability of the SA polymer chains, and then change the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency of DS was improved, and the burst release of DS was overcome. The factors (including concentration of Ca(2+), reaction time and temperature) affecting the growth of HA micro-particles have a clear influence on the entrapment efficiency and release rate of DS. In this work, the nanocomposite beads prepared under optimum condition could prolong the release of DS for 8h more compared with the pristine SA hydrogel beads.

Hyaluronic Acid Molecular Weight-Dependent Modulation of Mucin Nanostructure for Potential Mucosal Therapeutic Applications.

PubMed

Hansen, Irene M; Ebbesen, Morten F; Kaspersen, Liselotte; Thomsen, Troels; Bienk, Konrad; Cai, Yunpeng; Malle, Birgitte Mølholm; Howard, Kenneth A

2017-07-03

This study investigates the effects of different molecular weight hyaluronic acids (HAs) on the mucosal nanostructure using a pig stomach mucin hydrogel as a mucosal barrier model. Microparticles (1.0 μm) and nanoparticles (200 nm) were used as probes, and their movement in mucin was studied by a three-dimensional confocal microscopy-based particle tracking technique and by Nanoparticle Tracking Analysis (NTA) after addition of high-molecular weight (900 kDa) and low-molecular weight (33 kDa) HA. This demonstrated a molecular weight-dependent HA modulation of the mucin nanostructure with a 2.5-fold decrease in the mobility of 200 nm nanoparticles. To further investigate these mechanisms and to verify that the natural viscoelastic properties of mucus are not undesirably altered, rheological measurements were performed on mucin hydrogels with or without HA. This suggested the observed particle mobility restriction was not attributed to alterations of the natural mucin cohesive and viscoelastic properties but, instead, indicates that the added high-molecular weight HA primarily modulates the mucin nanostructure and mesh size. This study, hereby, demonstrates how mucus nanostructure can be modulated by the addition of high-molecular weight HA that offers an opportunity to control mucosal pathogenesis and drug delivery.

Three-dimensional prostate tumor model based on a hyaluronic acid-alginate hydrogel for evaluation of anti-cancer drug efficacy.

PubMed

Tang, Yadong; Huang, Boxin; Dong, Yuqin; Wang, Wenlong; Zheng, Xi; Zhou, Wei; Zhang, Kun; Du, Zhiyun

2017-10-01

In vitro cell-based assays are widely applied to evaluate anti-cancer drug efficacy. However, the conventional approaches are mostly based on two-dimensional (2D) culture systems, making it difficult to recapitulate the in vivo tumor scenario because of spatial limitations. Here, we develop an in vitro three-dimensional (3D) prostate tumor model based on a hyaluronic acid (HA)-alginate hybrid hydrogel to bridge the gap between in vitro and in vivo anticancer drug evaluations. In situ encapsulation of PCa cells was achieved by mixing HA and alginate aqueous solutions in the presence of cells and then crosslinking with calcium ions. Unlike in 2D culture, cells were found to aggregate into spheroids in a 3D matrix. The expression of epithelial to mesenchyme transition (EMT) biomarkers was found to be largely enhanced, indicating an increased invasion and metastasis potential in the hydrogel matrix. A significant up-regulation of proangiogenic growth factors (IL-8, VEGF) and matrix metalloproteinases (MMPs) was observed in 3D-cultured PCa cells. The results of anti-cancer drug evaluation suggested a higher drug tolerance within the 3D tumor model compared to conventional 2D-cultured cells. Finally, we found that the drug effect within the in vitro 3D cancer model based on HA-alginate matrix exhibited better predictability for in vivo drug efficacy.

A new route to fabricate biocompatible hydrogels with controlled drug delivery behavior.

PubMed

Hu, Xiaohong; Gong, Xiao

2016-05-15

Hydrogels for drug delivery have attracted extensive interests since they can be used for biomaterials such as contact lenses. Here, we report that biocompatible hydrogels for contact lenses with controlled drug delivery behavior can be fabricated using copolymer hydrogels and Layer-by-Layer (LbL) surface modification technique. Methyl acrylic anhydride (MAA) modified β-cyclodextrin (β-CD) (MA-β-CD) was synthesized and copolymerized with hydroxyethyl methacrylate (HEMA) to form copolymer hydrogel. The introduction of second monomer of MA-β-CD would accelerate the polymerization of hydrogel, leading to increase of residual CC groups. The structure of copolymers was characterized by differential scanning calorimetry (DSC). Transparence, equilibrium swelling ratio and contact angle of copolymer hydrogel were also detailed discussed in the work. In vitro drug release results showed that copolymer hydrogel with higher MA-β-CD content exhibited a better drug loading capacity and drug release behaviors could be tuned by MA-β-CD/monomer ratio. Finally, alkynyl functional hyaluronic acid (HA-BP) and nitrine functional chitosan (CS-N3) were synthesized and covalently cross-linked to copolymer hydrogel surface using LbL technique through click chemistry. The successful LbL multilayers were confirmed by X-ray Photoelectron Spectroscopy (XPS). Resultsofcytotoxicityexperiment revealed that the hydrogels were biocompatible since they could support the growth of cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Gene Delivery of TGF-β3 and BMP2 in an MSC-Laden Alginate Hydrogel for Articular Cartilage and Endochondral Bone Tissue Engineering.

PubMed

Gonzalez-Fernandez, Tomas; Tierney, Erica G; Cunniffe, Grainne M; O'Brien, Fergal J; Kelly, Daniel J

2016-05-01

Incorporating therapeutic genes into three-dimensional biomaterials is a promising strategy for enhancing tissue regeneration. Alginate hydrogels have been extensively investigated for cartilage and bone tissue engineering, including as carriers of transfected cells to sites of injury, making them an ideal gene delivery platform for cartilage and osteochondral tissue engineering. The objective of this study was to develop gene-activated alginate hydrogels capable of supporting nanohydroxyapatite (nHA)-mediated nonviral gene transfer to control the phenotype of mesenchymal stem cells (MSCs) for either cartilage or endochondral bone tissue engineering. To produce these gene-activated constructs, MSCs and nHA complexed with plasmid DNA (pDNA) encoding for transforming growth factor-beta 3 (pTGF-β3), bone morphogenetic protein 2 (pBMP2), or a combination of both (pTGF-β3-pBMP2) were encapsulated into alginate hydrogels. Initial analysis using reporter genes showed effective gene delivery and sustained overexpression of the transgenes were achieved. Confocal microscopy demonstrated that complexing the plasmid with nHA before hydrogel encapsulation led to transport of the plasmid into the nucleus of MSCs, which did not happen with naked pDNA. Gene delivery of TGF-β3 and BMP2 and subsequent cell-mediated expression of these therapeutic genes resulted in a significant increase in sulfated glycosaminoglycan and collagen production, particularly in the pTGF-β3-pBMP2 codelivery group in comparison to the delivery of either pTGF-β3 or pBMP2 in isolation. In addition, stronger staining for collagen type II deposition was observed in the pTGF-β3-pBMP2 codelivery group. In contrast, greater levels of calcium deposition were observed in the pTGF-β3- and pBMP2-only groups compared to codelivery, with a strong staining for collagen type X deposition, suggesting these constructs were supporting MSC hypertrophy and progression along an endochondral pathway. Together, these results suggest that the developed gene-activated alginate hydrogels were able to support transfection of encapsulated MSCs and directed their phenotype toward either a chondrogenic or an osteogenic phenotype depending on whether TGF-β3 and BMP2 were delivered in combination or isolation.

Hydrogel based QCM aptasensor for detection of avian influenza virus.

PubMed

Wang, Ronghui; Li, Yanbin

2013-04-15

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

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

PubMed

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

2016-12-01

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

78 FR 14963 - Foreign-Trade Zone 163-Ponce, Puerto Rico; Authorization of Production Activity; Zimmer...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-08

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [B-80-2012] Foreign-Trade Zone 163--Ponce, Puerto Rico; Authorization of Production Activity; Zimmer Manufacturing BV (Medical Devices); Ponce, Puerto... Subzone 163A, in Ponce, Puerto Rico. The notification was processed in accordance with the regulations of...

Novel enzymatically cross-linked hyaluronan hydrogels support the formation of 3D neuronal networks.

PubMed

Broguiere, Nicolas; Isenmann, Luca; Zenobi-Wong, Marcy

2016-08-01

Hyaluronan (HA) is an essential component of the central nervous system's extracellular matrix and its high molecular weight (MW) form has anti-inflammatory and anti-fibrotic properties relevant for regenerative medicine. Here, we introduce a new hydrogel based on high MW HA which is cross-linked using the transglutaminase (TG) activity of the activated blood coagulation factor XIII (FXIIIa). These HA-TG gels have significant advantages for neural tissue engineering compared to previous HA gels. Due to their chemical inertness in the absence of FXIIIa, the material can be stored long-term, is stable in solution, and shows no cytotoxicity. The gelation is completely cell-friendly due to the specificity of the enzyme and the gelation rate can be tuned from seconds to hours at physiological pH and independently of stiffness. The gels are injectable, and attach covalently to fibrinogen and fibrin, two common bioactive components in in vitro tissue engineering, as well as proteins present in vivo, allowing the gels to covalently bind to brain or spinal cord defects. These optimal chemical and bioactive properties of HA-TG gels enabled the formation of 3D neuronal cultures of unprecedented performance, showing fast neurite outgrowth, axonal and dendritic speciation, strong synaptic connectivity in 3D networks, and rapidly-occurring and long-lasting coordinated electrical activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hyaluronic acid for anticancer drug and nucleic acid delivery.

PubMed

Dosio, Franco; Arpicco, Silvia; Stella, Barbara; Fattal, Elias

2016-02-01

Hyaluronic acid (HA) is widely used in anticancer drug delivery, since it is biocompatible, biodegradable, non-toxic, and non-immunogenic; moreover, HA receptors are overexpressed on many tumor cells. Exploiting this ligand-receptor interaction, the use of HA is now a rapidly-growing platform for targeting CD44-overexpressing cells, to improve anticancer therapies. The rationale underlying approaches, chemical strategies, and recent advances in the use of HA to design drug carriers for delivering anticancer agents, are reviewed. Comprehensive descriptions are given of HA-based drug conjugates, particulate carriers (micelles, liposomes, nanoparticles, microparticles), inorganic nanostructures, and hydrogels, with particular emphasis on reports of preclinical/clinical results. Copyright © 2015 Elsevier B.V. All rights reserved.

Cytotoxicity testing of silver-containing burn treatments using primary and immortal skin cells.

PubMed

Boonkaew, Benjawan; Kempf, Margit; Kimble, Roy; Cuttle, Leila

2014-12-01

A novel burn wound hydrogel dressing has been previously developed which is composed of 2-acrylamido-2-methylpropane sulfonic acid sodium salt with silver nanoparticles (silver AMPS). This study compared the cytotoxicity of this dressing to the commercially available silver products; Acticoat™, PolyMem Silver(®) and Flamazine™ cream. Human keratinocytes (HaCaT and primary HEK) and normal human fibroblasts (NHF) were exposed to dressings incubated on Nunc™ polycarbonate inserts for 24, 48 and 72h. Four different cytotoxicity assays were performed including; Trypan Blue cell count, MTT, Celltiter-Blue™ and Toluidine Blue surface area assays. The results were expressed as relative cell viability compared to an untreated control. The cytotoxic effects of Acticoat™ and Flamazine™ cream were dependent on exposure time and cell type. After 24h exposure, Acticoat™ and Flamazine™ cream were toxic to all tested cell lines. Surprisingly, HaCaTs treated with Acticoat™ and Flamazine™ had an improved ability to survive at 48 and 72h while HEKs and NHFs had no improvement in survival with any treatment. The novel silver hydrogel and PolyMem Silver(®) showed low cytotoxicity to all tested cell lines at every time interval and these results support the possibility of using the novel silver hydrogel as a burn wound dressing. Researchers who rely on HaCaT cells as an accurate keratinocyte model should be aware that they can respond differently to primary skin cells. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

A Crosslinked HA-Based Hydrogel Ameliorates Dry Eye Symptoms in Dogs

PubMed Central

Williams, David L.; Mann, Brenda K.

2013-01-01

Keratoconjunctivitis sicca, commonly referred to as dry eye or KCS, can affect both humans and dogs. The standard of care in treating KCS typically includes daily administration of eye drops to either stimulate tear production or to hydrate and lubricate the corneal surface. Lubricating eye drops are often applied four to six times daily for the life of the patient. In order to reduce this dosing regimen yet still provides sufficient hydration and lubrication, we have developed a crosslinked hydrogel based on a modified, thiolated hyaluronic acid (HA), xCMHA-S. This xCMHA-S gel was found to have different viscosity and rheologic behavior than solutions of noncrosslinked HA. The gel was also able to increase tear breakup time in rabbits, indicating a stabilization of the tear film. Further, in a preliminary clinical study of dogs with KCS, the gel significantly reduced the symptoms associated with KCS within two weeks while only being applied twice daily. The reduction of symptoms combined with the low dosing regimen indicates that this gel may lead to both improved patient health and owner compliance in applying the treatment. PMID:23840213

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance

NASA Astrophysics Data System (ADS)

Asadnia, Mohsen; Kottapalli, Ajay Giri Prakash; Karavitaki, K. Domenica; Warkiani, Majid Ebrahimi; Miao, Jianmin; Corey, David P.; Triantafyllou, Michael

2016-09-01

We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices.

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance.

PubMed

Asadnia, Mohsen; Kottapalli, Ajay Giri Prakash; Karavitaki, K Domenica; Warkiani, Majid Ebrahimi; Miao, Jianmin; Corey, David P; Triantafyllou, Michael

2016-09-13

We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices.

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

PubMed

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

2018-02-01

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

In Vivo Engineering of the Vocal Fold ECM with Injectable HA Hydrogels -- Late Effects on Tissue Repair and Biomechanics in a Rabbit Model

PubMed Central

Klemuk, Sarah A.; Chen, Xia; Quinchia Johnson, Beatriz H.

2009-01-01

Objectives To determine if the utilization of injectable chemically-modified hyaluronan (HA) derivative at the time of intentional vocal fold resection may facilitate wound repair and preserve the unique viscoelastic properties of the extracellular matrix and lamina propria 6 months after treatment. Study Design Prospective, controlled animal study. Methods Twelve rabbit vocal folds were biopsied bilaterally, and the left side of vocal fold was treated with Extracel, an injectable, chemically-modified HA derivative, and the right side of vocal fold was injected with saline as control at the time of resection. Animals were sacrificed six months after biopsy and injection. Outcomes measured include transcription levels for procollagen, fibronectin, fibromodulin, TGF-β1, hyaluronan synthase and hyaluronidase and tissue biomechanics -- viscosity and elasticity. Results Extracel treated vocal folds were found to have significantly less fibrosis than saline treated controls. Extracel treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. Significantly decreased levels of fibronectin, fibromodulin, TGF-β1, procollagen I and hyaluronan synthase were measured. Conclusions Prophylactic in vivo manipulation of the extracellular matrix with an injectable HA hydrogel appears to induce vocal fold tissue regeneration to yield improved tissue composition and biomechanical properties at 6 months. PMID:20456912

Voice and Vision in Paul Zimmer's "The Great Bird of Love."

ERIC Educational Resources Information Center

Worsham, Fabian Clements

Paul Zimmer's latest poetry collection, "The Great Bird of Love," is serious and somber, fraught with the burden of evil, the indifference of God, and the certainty of death. The book is not humorless, however, as humor is central to both the chaotic evil and the ordered goodness of human life. It is in this collection that it is…

Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain.

PubMed

Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan

2016-04-01

Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Integration of Stem Cell to Chondrocyte-Derived Cartilage Matrix in Healthy and Osteoarthritic States in the Presence of Hydroxyapatite Nanoparticles.

PubMed

Dua, Rupak; Comella, Kristin; Butler, Ryan; Castellanos, Glenda; Brazille, Bryn; Claude, Andrew; Agarwal, Arvind; Liao, Jun; Ramaswamy, Sharan

2016-01-01

We investigated the effectiveness of integrating tissue engineered cartilage derived from human bone marrow derived stem cells (HBMSCs) to healthy as well as osteoarthritic cartilage mimics using hydroxyapatite (HA) nanoparticles immersed within a hydrogel substrate. Healthy and diseased engineered cartilage from human chondrocytes (cultured in agar gels) were integrated with human bone marrow stem cell (HBMSC)-derived cartilaginous engineered matrix with and without HA, and evaluated after 28 days of growth. HBMSCs were seeded within photopolymerizable poly (ethylene glycol) diacrylate (PEGDA) hydrogels. In addition, we also conducted a preliminary in vivo evaluation of cartilage repair in rabbit knee chondral defects treated with subchondral bone microfracture and cell-free PEGDA with and without HA. Under in vitro conditions, the interfacial shear strength between tissue engineered cartilage derived from HBMSCs and osteoarthritic chondrocytes was significantly higher (p < 0.05) when HA nanoparticles were incorporated within the HBMSC culture system. Histological evidence confirmed a distinct spatial transition zone, rich in calcium phosphate deposits. Assessment of explanted rabbit knees by histology demonstrated that cellularity within the repair tissues that had filled the defects were of significantly higher number (p < 0.05) when HA was used. HA nanoparticles play an important role in treating chondral defects when osteoarthritis is a co-morbidity. We speculate that the calcified layer formation at the interface in the osteoarthritic environment in the presence of HA is likely to have attributed to higher interfacial strength found in vitro. From an in vivo standpoint, the presence of HA promoted cellularity in the tissues that subsequently filled the chondral defects. This higher presence of cells can be considered important in the context of accelerating long-term cartilage remodeling. We conclude that HA nanoparticles play an important role in engineered to native cartilage integration and cellular processes.

3D‐Bioprinted Osteoblast‐Laden Nanocomposite Hydrogel Constructs with Induced Microenvironments Promote Cell Viability, Differentiation, and Osteogenesis both In Vitro and In Vivo

PubMed Central

Zhai, Xinyun; Ma, Yufei; Cheng, Delin; Wu, Mingming; Liu, Wenguang; Zhao, Xiaoli

2017-01-01

Abstract An osteoblast‐laden nanocomposite hydrogel construct, based on polyethylene glycol diacrylate (PEGDA)/laponite XLG nanoclay ([Mg5.34Li0.66Si8O20(OH)4]Na0.66, clay)/hyaluronic acid sodium salt (HA) bio‐inks, is developed by a two‐channel 3D bioprinting method. The novel biodegradable bio‐ink A, comprised of a poly(ethylene glycol) (PEG)–clay nanocomposite crosslinked hydrogel, is used to facilitate 3D‐bioprinting and enables the efficient delivery of oxygen and nutrients to growing cells. HA with encapsulated primary rat osteoblasts (ROBs) is applied as bio‐ink B with a view to improving cell viability, distribution uniformity, and deposition efficiency. The cell‐laden PEG–clay constructs not only encapsulated osteoblasts with more than 95% viability in the short term but also exhibited excellent osteogenic ability in the long term, due to the release of bioactive ions (magnesium ions, Mg2+ and silicon ions, Si4+), which induces the suitable microenvironment to promote the differentiation of the loaded exogenous ROBs, both in vitro and in vivo. This 3D‐bioprinting method holds much promise for bone tissue regeneration in terms of cell engraftment, survival, and ultimately long‐term function. PMID:29593958

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance

PubMed Central

Asadnia, Mohsen; Kottapalli, Ajay Giri Prakash; Karavitaki, K. Domenica; Warkiani, Majid Ebrahimi; Miao, Jianmin; Corey, David P.; Triantafyllou, Michael

2016-01-01

We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices. PMID:27622466

Viscosupplementation for Osteoarthritis of the Knee: A Key Opinion Leader Panel Discussion.

PubMed

Bert, Jack; Kenney, Jim; Sgaglione, Nicholas A; McClelland, Scott; Brophy, Robert; Toth, John; Ruane, Joseph; Ali, Yousaf; Arquette, Sheila; Dasa, Vinod; Lopes, Maria

2018-06-01

With a sharp rise in the prevalence of osteoarthritis of the knee (OAK) in a younger population, new management strategies are needed to preserve mobility, improve patients' quality of life, and reduce the effects of potential disease-related comorbidities. Viscosupplementation with the use of hyaluronic acid (HA) injection is a treatment option for OAK that can provide lubrication and elastic shock absorption, leading to potential pain relief, improved function, and reduced stiffness. A key opinion leader (KOL) panel discussion was held December 3, 2016, with the objective of sharing opinions, ideas, information, and trends regarding OAK and the potential treatment and management offered by viscosupplementation. The panel concluded that viscosupplementation with HA injections presents a viable, cost-effective, and safe alternative for the treatment of OAK. This panel discussion and report was facilitated by Magellan Rx Manage-ment and funded by Sanofi. Bert and Ruane report fees from Sanofi outside of this project. Sgaglione reports royalty payments from Zimmer Biomet and Wolters Kluwer. Dasa has received fees from Bioventus and Myoscience. All the authors received an honorarium for work on this project. Lopes is employed by Magellan Rx Management.

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

PubMed Central

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

2016-01-01

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

Hydrogels with Spatially and Temporally Controlled Properties to Control Cellular Interactions

NASA Astrophysics Data System (ADS)

Burdick, Jason

2011-03-01

Stem cells (e.g., mesenchymal stem cells, MSCs) respond to many cues from their microenvironment, which may include chemical signals, mechanics, and topography. Importantly, these cues may be incorporated into scaffolding to control stem cell differentiation and optimize their ability to produce tissues in regenerative medicine. Despite the significant amount of work in this area, the materials have been primarily static and uniform. To this end, we have developed a sequential crosslinking process that relies on our ability to crosslinked functional biopolymers (e.g., methacrylated hyaluronic acid, HA) in two steps, namely a Michael-type addition reaction to partially consume reactive groups and then a light-initiated free-radical polymerization to further crosslink the material. With light exposure during the second step comes control over the material in space (via masks and lasers) and time (via intermittent light exposure). We are applying this technique for numerous applications. For example, when the HA hydrogels are crosslinked with MMP degradable peptides with thiol termini during the first step, a material that can be degraded by cells is obtained. However, cell-mediated degradation is obstructed with the introduction of kinetic chains during the second step, leading to spatially controlled cell degradability. Due to the influence of cellular spreading on MSC differentiation, we have controlled cell fates by controlling their spread ability, for instance towards osteoblasts in spread areas and adipocytes when cell remained rounded. We are also using the process of stiffening with time to investigate mechanically induced differentiation, particularly in materials with evolving mechanics. Overall, these advanced HA hydrogels provide us the opportunity to investigate diverse and controlled material properties on MSC interactions.

Synthesis and characterization of a Hyaluronan-polyethylene copolymer for biomedical applications.

PubMed

Oldinski, Rachael A; Cranson, Cody N; James, Susan P

2010-08-01

Hyaluronan (HA)-based biomaterials are of interest for bone and cartilage tissue engineering because HA plays an important role in orthopedic tissue development, function, and repair. The goal of this project was to develop a biomaterial that incorporated the constituents of both a hydrogel and a hydrophobic polymer for biomedical applications. A series of amphiphilic graft copolymers consisting of HA, a glycosaminoglycan, and high-density polyethylene (HDPE), that is, HA-co-HDPE, were fabricated. The chemical characteristics, physical and viscoelastic properties, and cytocompatibility of novel HA-co-HDPE materials were characterized via Fourier Transform infrared (FTIR) spectroscopy, solid state nuclear magnetic resonance (ssNMR) spectroscopy, differential scanning calorimetry (DSC), dynamic shear testing, and an in vitro human osteoblast cell study. The esterification reaction between HA and functionalized HDPE resulted in semicrystalline, insoluble powder. The dynamic shear properties of HA-co-HDPE concentrated solutions were more like natural proteoglycans than the HA control. HA-co-HDPE was successfully compression molded into disks that swelled upon hydration. Osteoblasts were viable and expressed the osteoblast phenotype after 7 days of culture on HA-co-HDPE materials. These HA-co-HDPE materials may have several biomaterial applications in saline suspension or molded form, including orthopedic tissue repair.

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

NASA Astrophysics Data System (ADS)

Morozova, Svetlana; Muthukumar, Murugappan

2015-03-01

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

Mechanistic Analysis of Human Skin Distribution and Follicular Targeting of Adapalene-Loaded Biodegradable Nanospheres With an Insight Into Hydrogel Matrix Influence, In Vitro Skin Irritation, and In Vivo Tolerability.

PubMed

Sallam, Marwa Ahmed; Marín Boscá, María Teresa

2017-10-01

This work aimed at the development of a biocompatible, non-oily nanomedicine for follicular delivery of adapalene (AD) ameliorating its irritation potential for convenient localized topical treatment of acne vulgaris. AD was efficiently incorporated into poly-ε-caprolactone nanospheres (NS) with an encapsulation efficiency of 84.73% ± 1.52%, a particle size of 107.5 ± 8.19 nm, and zeta potential of -13.1 mV demonstrating a sustained-release behavior. The AD-NS were embedded in either hydroxypropyl methylcellulose (HPMC) or hyaluronate (HA) gel. The ex vivo human skin dermatokinetics of AD from each system was studied. The nanoparticles dispersion showed significantly higher AD retention in the epidermis and dermis than AD suspension. NS-HPMC decreased whereas NS-HA increased AD retained in all the skin layers. The fate of the NS and the role of the hydrogel in modulating skin distribution was evaluated by confocal laser scanning microscopy (CLSM) imaging of fluorescently labeled NS. CLSM illustrated follicular localization of the florescent NS. HPMC gel restricted the presence of NS to the stratum corneum and epidermis. HA gel enhanced the penetration of NS to all the skin layers. In vitro skin irritation using human dermal fibroblasts and in vivo animal tolerability studies were performed. Accordingly, HA gel-dispersed AD-NS presented a nonirritant compromised cosmeceutical formulation suitable for oily acneic skin. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Riboflavin-induced photo-crosslinking of collagen hydrogel and its application in meniscus tissue engineering.

PubMed

Heo, Jiseung; Koh, Rachel H; Shim, Whuisu; Kim, Hwan D; Yim, Hyun-Gu; Hwang, Nathaniel S

2016-04-01

A meniscus tear is a common knee injury, but its regeneration remains a clinical challenge. Recently, collagen-based scaffolds have been applied in meniscus tissue engineering. Despite its prevalence, application of natural collagen scaffold in clinical setting is limited due to its extremely low stiffness and rapid degradation. The purpose of the present study was to increase the mechanical properties and delay degradation rate of a collagen-based scaffold by photo-crosslinking using riboflavin (RF) and UV exposure. RF is a biocompatible vitamin B2 that showed minimal cytotoxicity compared to conventionally utilized photo-initiator. Furthermore, collagen photo-crosslinking with RF improved mechanical properties and delayed enzyme-triggered degradation of collagen scaffolds. RF-induced photo-crosslinked collagen scaffolds encapsulated with fibrochondrocytes resulted in reduced scaffold contraction and enhanced gene expression levels for the collagen II and aggrecan. Additionally, hyaluronic acid (HA) incorporation into photo-crosslinked collagen scaffold showed an increase in its retention. Based on these results, we demonstrate that photo-crosslinked collagen-HA hydrogels can be potentially applied in the scaffold-based meniscus tissue engineering.

Genome and transcriptome studies of the protozoan parasites Trypanosoma cruzi and Giardia intestinalis

NASA Astrophysics Data System (ADS)

Farran, Alexandra J. E.

Vocal fold (VF) diseases and disorders are difficult to treat surgically or therapeutically. Tissue engineering offers an alternative strategy for the restoration of functional VF. In this work, we have developed tissue engineering methodologies for the functional reconstruction of VF. As a first step, the structure, composition and mechanical properties of native VF tissues have been investigated. In pigs ranging from fetal to 2+ years old, the VF structure and viscoelastic properties were found to be age-dependent. Adult tissues were more organized, displaying a denser lamina propria, and mature elastin fibers compared to fetal tissues, resulting in higher storage moduli. Secondly, biomimetic scaffolds which recaptured the mechanical properties of the native VF were developed. Chemically-defined collagen-hyaluronic acid (HA) composite hydrogels, and elastin-mimetic hybrid polymers (EMHPs) were successfully used as conducive 3D matrices, and 2D elastic scaffolds respectively, to in vitro static culture of fibroblasts. While the collagen-HA hydrogels allowed for in situ cell encapsulation and supported cell attachment and proliferation in 3D, the integrin-binding domain RGDSP was needed for cell proliferation on EMHPs. To emulate in vitro the mechanical environment of the native VF tissue, a dynamic culture system capable of generating vibratory stimulations at human phonation frequencies was successfully created and characterized. Gene expression analysis of fibroblasts subjected to 1 hour vibrations in 2D revealed that the expression of ECM-related genes was altered in response to changes in vibratory frequency and amplitude. Finally, expanding on our previous studies, the dynamic culture system was modified to accommodate for the long-term dynamic culture of cell-laden hydrogels. Human mesenchymal stem cells (hMSCs) encapsulated in a collagen/HA-based hydrogel, cultured in presence of connective tissue growth factor (CTGF), and subjected to high frequency vibrations were shown to respond to all three type of external factors. In summary, microenvironments such as biomimetic scaffolds, soluble factors, and mechanical stimuli are important modulator of cellular function. The strategic combination of those microenvironments into a biomimicking VF tissue engineering 3D system did not only provide an in vitro platform for the investigation of VF diseases, but also have the potential to offer alternative treatments for VF disorders.

Hyaluronic acid-laminin hydrogels increase neural stem cell transplant retention and migratory response to SDF-1α.

PubMed

Addington, C P; Dharmawaj, S; Heffernan, J M; Sirianni, R W; Stabenfeldt, S E

2017-07-01

The chemokine SDF-1α plays a critical role in mediating stem cell response to injury and disease and has specifically been shown to mobilize neural progenitor/stem cells (NPSCs) towards sites of neural injury. Current neural transplant paradigms within the brain suffer from low rates of retention and engraftment after injury. Therefore, increasing transplant sensitivity to injury-induced SDF-1α represents a method for increasing neural transplant efficacy. Previously, we have reported on a hyaluronic acid-laminin based hydrogel (HA-Lm gel) that increases NPSC expression of SDF-1α receptor, CXCR4, and subsequently, NPSC chemotactic migration towards a source of SDF-1α in vitro. The study presented here investigates the capacity of the HA-Lm gel to promote NPSC response to exogenous SDF-1α in vivo. We observed the HA-Lm gel to significantly increase NPSC transplant retention and migration in response to SDF-1α in a manner critically dependent on signaling via the SDF-1α-CXCR4 axis. This work lays the foundation for development of a more effective cell therapy for neural injury, but also has broader implications in the fields of tissue engineering and regenerative medicine given the essential roles of SDF-1α across injury and disease states. Copyright © 2016 Elsevier B.V. All rights reserved.

3D Printing Surgical Implants at the clinic: A Experimental Study on Anterior Cruciate Ligament Reconstruction

PubMed Central

Liu, An; Xue, Guang-huai; Sun, Miao; Shao, Hui-feng; Ma, Chi-yuan; Gao, Qing; Gou, Zhong-ru; Yan, Shi-gui; Liu, Yan-ming; He, Yong

2016-01-01

Desktop three-dimensional (3D) printers (D3DPs) have become a popular tool for fabricating personalized consumer products, favored for low cost, easy operation, and other advantageous qualities. This study focused on the potential for using D3DPs to successfully, rapidly, and economically print customized implants at medical clinics. An experiment was conducted on a D3DP-printed anterior cruciate ligament surgical implant using a rabbit model. A well-defined, orthogonal, porous PLA screw-like scaffold was printed, then coated with hydroxyapatite (HA) to improve its osteoconductivity. As an internal fixation as well as an ideal cell delivery system, the osteogenic scaffold loaded with mesenchymal stem cells (MSCs) were evaluated through both in vitro and in vivo tests to observe bone-ligament healing via cell therapy. The MSCs suspended in Pluronic F-127 hydrogel on PLA/HA screw-like scaffold showed the highest cell proliferation and osteogenesis in vitro. In vivo assessment of rabbit anterior cruciate ligament models for 4 and 12 weeks showed that the PLA/HA screw-like scaffold loaded with MSCs suspended in Pluronic F-127 hydrogel exhibited significant bone ingrowth and bone-graft interface formation within the bone tunnel. Overall, the results of this study demonstrate that fabricating surgical implants at the clinic (fab@clinic) with D3DPs can be feasible, effective, and economical. PMID:26875826

Effect of negatively charged cellulose nanofibers on the dispersion of hydroxyapatite nanoparticles for scaffolds in bone tissue engineering.

PubMed

Park, Minsung; Lee, Dajung; Shin, Sungchul; Hyun, Jinho

2015-06-01

Nanofibrous 2,2,6,6-tetramethylpiperidine-1-oxyl(TEMPO)-oxidized bacterial cellulose (TOBC) was used as a dispersant of hydroxyapatite (HA) nanoparticles in aqueous solution. The surfaces of TOBC nanofibers were negatively charged after the reaction with the TEMPO/NaBr/NaClO system at pH 10 and room temperature. HA nanoparticles were simply adsorbed on the TOBC nanofibers (HA-TOBC) and dispersed well in DI water. The well-dispersed HA-TOBC colloidal solution formed a hydrogel after the addition of gelatin, followed by crosslinking with glutaraldehyde (HA-TOBC-Gel). The chemical modification of the fiber surfaces and the colloidal stability of the dispersion solution confirmed TOBC as a promising HA dispersant. Both the Young's modulus and maximum tensile stress increased as the amount of gelatin increased due to the increased crosslinking of gelatin. In addition, the well-dispersed HA produced a denser scaffold structure resulting in the increase of the Young's modulus and maximum tensile stress. The well-developed porous structures of the HA-TOBC-Gel composites were incubated with Calvarial osteoblasts. The HA-TOBC-Gel significantly improved cell proliferation as well as cell differentiation confirming the material as a potential candidate for use in bone tissue engineering scaffolds. Copyright © 2015 Elsevier B.V. All rights reserved.

Rapid engineering of endothelial cell-lined vascular-like structures in in situ crosslinkable hydrogels.

PubMed

Kageyama, Tatsuto; Kakegawa, Takahiro; Osaki, Tatsuya; Enomoto, Junko; Ito, Taichi; Nittami, Tadashi; Fukuda, Junji

2014-06-01

Fabrication of perfusable vascular networks in vitro is one of the most critical challenges in the advancement of tissue engineering. Because cells consume oxygen and nutrients during the fabrication process, a rapid fabrication approach is necessary to construct cell-dense vital tissues and organs, such as the liver. In this study, we propose a rapid molding process using an in situ crosslinkable hydrogel and electrochemical cell transfer for the fabrication of perfusable vascular structures. The in situ crosslinkable hydrogel was composed of hydrazide-modified gelatin (gelatin-ADH) and aldehyde-modified hyaluronic acid (HA-CHO). By simply mixing these two solutions, the gelation occurred in less than 20 s through the formation of a stable hydrazone bond. To rapidly transfer cells from a culture surface to the hydrogel, we utilized a zwitterionic oligopeptide, which forms a self-assembled molecular layer on a gold surface. Human umbilical vein endothelial cells adhering on a gold surface via the oligopeptide layer were transferred to the hydrogel within 5 min, along with electrochemical desorption of the oligopeptides. This approach was applicable to cylindrical needles 200-700 µm in diameter, resulting in the formation of perfusable microchannels where the internal surface was fully enveloped with the transferred endothelial cells. The entire fabrication process was completed within 10 min, including 20 s for the hydrogel crosslinking and 5 min for the electrochemical cell transfer. This rapid fabrication approach may provide a promising strategy to construct perfusable vasculatures in cell-dense tissue constructs and subsequently allow cells to organize complicated and fully vascularized tissues while preventing hypoxic cell injury.

Hyaluronic acid affects the in vitro induction effects of Synthetic PAMPS and PDMAAm hydrogels on chondrogenic differentiation of ATDC5 cells, depending on the level of concentration

PubMed Central

2013-01-01

Background It has been a common belief that articular cartilage tissue cannot regenerate in vivo. Recently, however, we have found that spontaneous hyaline cartilage regeneration can be induced in vivo by implanting a synthetic double-network (DN) hydrogel, which is composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) and poly-(N,N’-dimethyl acrylamide) (PDMAAm). However, the mechanism of this phenomenon has not been clarified. Recently, we have found that single-network PAMPS and PDMAAm gels can induce chondrogenic differentiation of ATDC5 cells in vitro even in a maintenance medium. In the in vivo condition, there is a strong possibility that the induction effect of the gel itself is enhanced by some molecules which exist in the joint. We have noticed that the joint fluid naturally contains hyaluronic acid (HA). The purpose of this study is to clarify in vitro effects of supplementation of HA on the differentiation effect of the PAMPS and PDMAAm gels. Methods We cultured the ATDC5 cells on the PAMPS gel, the PDMAAm gel, and the polystyrene (PS) dish surface with the maintenance medium without insulin for 7 days. HA having a molecular weight of approximately 800 kDa was supplemented into the medium so that the concentration became 0.00, 0.01, 0.10, or 1.00 mg/mL. We evaluated the cultured cells with phase-contrast microscopy and PCR analyses. Results On the PAMPS gel, supplementation with HA of 0.01 and 0.10 mg/mL significantly increased expression of type-2 collagen mRNA (p = 0.0008 and p = 0.0413) and aggrecan mRNA (p = 0.0073 and p = 0.0196) than that without HA. On the PDMAAm gel, supplementation with HA of 1.00 mg/mL significantly reduced expression of these genes in comparison with the culture without HA (p = 0.0426 and p = 0.0218). Conclusions The in vitro induction effects of the PAMPS and PDMAAm gels on chondrogenic differentiation of ATDC5 cells are significantly affected by HA, depending on the level of concentration. These results suggested that there is a high possibility that HA plays an important role in the in vivo spontaneous hyaline cartilage regeneration phenomenon induced by the PAMPS/PDMAAm DN gel. PMID:23379610

Efficacy of two different thiol-modified crosslinked hyaluronate formulations as vitreous replacement compared to silicone oil in a model of retinal detachment

PubMed Central

Schnichels, Sven; Schneider, Nele; Hohenadl, Christine; Hurst, José; Schatz, Andreas; Januschowski, Kai; Spitzer, Martin S.

2017-01-01

The efficacy of two novel artificial vitreous body substitutes (VBS) consisting of highly biocompatible thiolated cross-linked hyaluronic acid (HA)-based hydrogels in comparison to silicone oil in a model of retinal detachment was investigated. Pars plana vitrectomy (23G) was performed in the right eye of 24 pigmented rabbits. Retinal detachment of two quadrants was induced by creating a small retinotomy near the vascular arcade and injecting balanced salt solution (BSS) subretinally. The retina was reattached by injecting air, which was followed by increasing the infusion pressure, and the retinal tear was treated by endolaser photocoagulation. At the end of the procedure, the eye was filled either with 5000-cs silicone oil (after fluid air exchange) or the respective hydrogel (with two different viscosities). Follow-up examination included slit lamp examination, funduscopy, intraocular pressure measurements (IOP), optical coherence tomography (OCT) and electroretinogram (ERG) measurements. After a maximum follow-up of four weeks both eyes were removed, examined macroscopically, photographed, and prepared for histology. Of the eight rabbits that received silicone oil, seven (87.5%) developed a recurrent retinal detachment with pronounced proliferative vitreoretinopathy within the first two weeks after surgery. In contrast, in the hydrogel treated eyes, the retina stayed attached in the majority of the cases (73.3%). IOP and retinal morphology were normal as long as the retina remained re-attached. In conclusions, this model of retinal detachment, both thiolated crosslinked hyaluronate hydrogels showed superior efficacy when compared to silicone oil. These hydrogels have a promising potential as novel vitreous body substitutes. PMID:28248989

Cytoprotection: Immune and Matrix Modulation of Tissue Repair

DTIC Science & Technology

2011-04-14

the damaged external urethral sphincter and significantly improved VLPP. Poster #BS39 THE EFFECT OF DONOR AGE ON INDUCED PLURIPOTENT STEM CELLS FROM...is an extracellular matrix hydrogel that contains cross-linked HMW-HA, which has been used to advantage in the growth of other stem cell types, but...that, after treatment with regenerating or reconstituted cells or stem cells , the viability of those therapeutic cells is often threatened by the

An In Vivo Study of Composite Microgels Based on Hyaluronic Acid and Gelatin for the Reconstruction of Surgically Injured Rat Vocal Folds

ERIC Educational Resources Information Center

Coppoolse, Jiska M. S.; Van Kooten, T. G.; Heris, Hossein K.; Mongeau, Luc; Li, Nicole Y. K.; Thibeault, Susan L.; Pitaro, Jacob; Akinpelu, Olubunm; Daniel, Sam J.

2014-01-01

Purpose: The objective of this study was to investigate local injection with a hierarchically microstructured hyaluronic acid-gelatin (HA-Ge) hydrogel for the treatment of acute vocal fold injury using a rat model. Method: Vocal fold stripping was performed unilaterally in 108 Sprague-Dawley rats. A volume of 25 µl saline (placebo controls),…

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 cells were identified in cultured cells from dispersed tissue. Biomarker studies with the salivary enzyme, alpha-amylase, and tight junction proteins, such as zonula occludens-1 and E-cadherin, confirmed the phenotype of these cells. Strong staining for laminin and perlecan/HSPG2 were noted in basement membranes and perlecan also was secreted and organized by cultured acinar populations, which formed lobular structures that mimicked intact glands when cultured on Matrigel(TM) or a bioactive peptide derived from domain IV of perlecan (PlnDIV). On either matrix, large acini-like lobular structures grew and formed connections between the lobes. alpha-Amylase secretion was confirmed by staining and activity assay. Biomarkers including tight junction protein E-cadherin and water channel protein, aquaporin 5 (AQP5) found in tissue, were expressed in cultured acinar cells. Cells cultured on Matrigel(TM) or PlnDIV peptide organized stress fibers and activated focal adhesion kinase (FAK). HA, a natural polysaccharide and a major component of the ECM, can be used to generate soft and pliable hydrogels. A culture system consisting of HA hydrogel and PlnDIV peptide was used to generate a 2.5D culture system. Acinar cells cultured on these hydrogels self-assembled into lobular structures and expressed tight junction components such as ZO-1. Acini-like structures were stained for the presence of alpha-amylase. Live/dead staining revealed the presence of apoptotic cells in the center of the acini-like structures, indicative of lumen formation. The functionality of these acini-like structures was studied by stimulating them with neurotransmitters to enhance their fluid and protein production. Acini-like structures treated with norepinephrine and isoproterenol showed increased granule formation as observed by phase contrast microscopy and alpha-amylase staining in the structures. Lobular structures on hydrogels were treated with acetylcholine to increase fluid production. The increase in intracellular calcium due to the activation of the M3 muscarinic receptor via binding to acetylcholine was measured. Although cells in 2D did not show any differences, cells on the 2.5D hydrogels showed an increase in intracellular calcium. The culture system consisting of PlnDIV peptide reported here will aid the development of an artificial salivary gland which will foster formation of functional salivary units capable of secreting salivary fluid and which can be implanted into patients to relieve xerostomia. Future experiments will involve implantation of these hydrogels in animal models to test their functionality in vivo.

Experimental and numerical measurements of adhesion energies between PHEMA and PGLYMA with hydroxyapatite crystal.

PubMed

Youssefian, Sina; Liu, Pingsheng; Askarinejad, Sina; Shalchy, Faezeh; Song, Jie; Rahbar, Nima

2015-07-16

Synthetic orthopaedic materials consisting of a single bioinert polymeric material do not meet the complex biological and physical requirements of scaffold-guided bone tissue repair and regeneration. Of particular interest is the design of biocompatible hydrogel-hydroxyapatite composite bone substitutes with outstanding interfacial adhesion that would warranty the ability for the composite to withstand functional loadings without exhibiting brittle fractures during the dynamic guided tissue regeneration. For this purpose, the hydroxylated side chain of chemically cross-linked poly (2-hydroxyethyl methacrylate) (pHEMA) is substitute with a carboxylated side chain to make poly (glycerol methacrylate) (pGLYMA). Here, we carry out atomistic simulations and atomic force microscopy to predict and experimentally determine the interfacial adhesion energies of pHEMA and pGLYMA with the surface of single-crystalline hydroxyapatite (HA) whiskers. Both experimental and numerical results showed that pGLYMA has stronger adhesion forces with HA and may be used for preparing a high-affinity polymer-HA composite. The high adhesive interactions between pGLYMA and HA were found to be due to strong electrostatic energies.

Functionalized scaffolds to enhance tissue regeneration

PubMed Central

Guo, Baolin; Lei, Bo; Li, Peng; Ma, Peter X.

2015-01-01

Tissue engineering scaffolds play a vital role in regenerative medicine. It not only provides a temporary 3-dimensional support during tissue repair, but also regulates the cell behavior, such as cell adhesion, proliferation and differentiation. In this review, we summarize the development and trends of functional scaffolding biomaterials including electrically conducting hydrogels and nanocomposites of hydroxyapatite (HA) and bioactive glasses (BGs) with various biodegradable polymers. Furthermore, the progress on the fabrication of biomimetic nanofibrous scaffolds from conducting polymers and composites of HA and BG via electrospinning, deposition and thermally induced phase separation is discussed. Moreover, bioactive molecules and surface properties of scaffolds are very important during tissue repair. Bioactive molecule-releasing scaffolds and antimicrobial surface coatings for biomedical implants and scaffolds are also reviewed. PMID:25844177

Development of soy lecithin based novel self-assembled emulsion hydrogels.

PubMed

Singh, Vinay K; Pandey, Preeti M; Agarwal, Tarun; Kumar, Dilip; Banerjee, Indranil; Anis, Arfat; Pal, Kunal

2015-03-01

The current study reports the development and characterization of soy lecithin based novel self-assembled emulsion hydrogels. Sesame oil was used as the representative oil phase. Emulsion gels were formed when the concentration of soy lecithin was >40% w/w. Metronidazole was used as the model drug for the drug release and the antimicrobial tests. Microscopic study showed the apolar dispersed phase in an aqueous continuum phase, suggesting the formation of emulsion hydrogels. FTIR study indicated the formation of intermolecular hydrogen bonding, whereas, the XRD study indicated predominantly amorphous nature of the emulsion gels. Composition dependent mechanical and drug release properties of the emulsion gels were observed. In-depth analyses of the mechanical studies were done using Ostwald-de Waele power-law, Kohlrausch and Weichert models, whereas, the drug release profiles were modeled using Korsmeyer-Peppas and Peppas-Sahlin models. The mechanical analyses indicated viscoelastic nature of the emulsion gels. The release of the drug from the emulsion gels was diffusion mediated. The drug loaded emulsion gels showed good antimicrobial activity. The biocompatibility test using HaCaT cells (human keratinocytes) suggested biocompatibility of the emulsion gels. Copyright © 2015 Elsevier Ltd. All rights reserved.

Septicemia

MedlinePlus

Blood poisoning; Bacteremia with sepsis ... Shapiro NI, Zimmer GD, Barkin AZ. Sepsis syndromes. In: Marx, JA, Hockberger RS, Walls RM, et al, eds. Rosen's Emergency Medicine: Concepts and Clinical Practice . 8th ed. Philadelphia, PA: ...

Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink

PubMed Central

Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D.; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

2016-01-01

Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types. PMID:27166839

Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink.

PubMed

Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

2016-04-21

Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types.

Business Ownership and Management.

ERIC Educational Resources Information Center

Kaser, Ken, Ed.

1991-01-01

Includes five articles: "Women in Management" (Zimmerer); "Business Boot Camp (interviews with young entrepreneurs)" (Kaser); "Plan Your Own Business Project" (Kohns); "Business Education and the Middle Level Student" (Patterson, Leblanc); and "Small Business Ownership Planning" (Fiber). (SK)

Transdermal gelation of methacrylated macromers with near-infrared light and gold nanorods

NASA Astrophysics Data System (ADS)

Gramlich, William M.; Holloway, Julianne L.; Rai, Reena; Burdick, Jason A.

2014-01-01

Injectable hydrogels provide locally controlled tissue bulking and a means to deliver drugs and cells to the body. The formation of hydrogels in vivo may involve the delivery of two solutions that spontaneously crosslink when mixed, with pH or temperature changes, or with light (e.g., visible or ultraviolet). With these approaches, control over the kinetics of gelation, introduction of the initiation trigger (e.g., limited penetration of ultraviolet light through tissues), or alteration of the material physical properties (e.g., mechanics) may be difficult to achieve. To overcome these limitations, we used the interaction of near-infrared (NIR) light with gold nanorods (AuNRs) to generate heat through the photothermal effect. NIR light penetrates tissues to a greater extent than other wavelengths and provides a means to indirectly initiate radical polymerization. Specifically, this heating coupled with a thermal initiator (VA-044) produced radicals that polymerized methacrylated hyaluronic acid (MeHA) and generated hydrogels. A range of VA-044 concentrations changed the gelation time, yielding a system stable at 37 ° C for 22 min that gels quickly (˜3 min) when heated to 55 ° C. With a constant irradiation time (10 min) and laser power (0.3 W), different VA-044 and AuNR concentrations tuned the compressive modulus of the hydrogel. By changing the NIR irradiation time we attained a wide range of moduli at a set solution composition. In vivo mouse studies confirmed that NIR laser irradiation through tissue could gel an injected precursor solution transdermally.

A State-of-the-Art Contamination Effects Research and Test Facility

NASA Technical Reports Server (NTRS)

Olson, Keith R.; Folgner, Kelsey A.; Barrie, James D.; Villahermosa, Randy M.

2008-01-01

In the ongoing effort to better understand various spacecraft contamination phenomena, a new state of the art contamination effects research and test facility was designed, and recently brought on-line at The Aerospace Corporation s Space Materials Laboratory. This high vacuum test chamber employs multiple in-situ analytical techniques, making it possible to study both the qualitative and quantitative aspects of contaminant film formation in the presence or absence of VUV radiation. Adsorption and desorption kinetics, "photo-fixing efficiency", transmission loss of uniform contaminant films, light scatter from non-uniform films, and film morphology have been studied in this facility. This paper describes this new capability in detail and presents data collected from several of the analytical instruments.

Secretary Chu visits Argonne—Groundbreaking ceremony for new Energy Sciences building

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

Isaacs, Eric; Zimmer, Robert; Durbin, Dick

2011-01-01

U.S. Department of Energy Secretary Steven Chu, joined Senator Richard Durbin, University of Chicago President Robert Zimmer and Argonne Director Eric Isaacs to break ground for Argonne's new Energy and Sciences building.

A novel poloxamers/hyaluronic acid in situ forming hydrogel for drug delivery: rheological, mucoadhesive and in vitro release properties.

PubMed

Mayol, Laura; Quaglia, Fabiana; Borzacchiello, Assunta; Ambrosio, Luigi; La Rotonda, Maria I

2008-09-01

The influence of hyaluronic acid (HA) on the gelation properties of poloxamers blends has been studied with the aim of engineering thermosensitive and mucoadhesive polymeric platforms for drug delivery. The gelation temperature (T(gel)), viscoelastic properties and mucoadhesive force of the systems were investigated and optimised by means of rheological analyses. Poloxamers micellar diameter was evaluated by photon correlation spectroscopy (PCS). Moreover in order to explore the feasibility of these platforms for drug delivery, the optimised systems were loaded with acyclovir and its release properties studied in vitro. By formulating poloxamers/HA platforms, at specific concentrations, it was possible to obtain a thermoreversible gel with a T(gel) close to body temperature. The addition of HA did not hamper the self assembling process of poloxamers just delaying the gelation temperature of few Celsius degrees. Furthermore, HA presence led to a strong increase of the poloxamer rheological properties thus indicating possible HA interactions with micelles through secondary bonds, such as hydrogen ones, which reinforce the gel structure. These interactions could also explain PCS results which show, in systems containing HA, aggregates with hydrodynamic diameters much higher than those of poloxamer micelles. Mucoadhesion experiments showed a rheological synergism between poloxamers/HA gels and mucin dispersion which led to a change of the flow behaviour from a quite Newtonian one of the separate solutions to a pseudoplastic one of their mixture. In vitro release experiments indicated that the optimised platform was able to prolong and control acyclovir release for more than 6h.

Engineering a biomimetic three-dimensional nanostructured bone model for breast cancer bone metastasis study.

PubMed

Zhu, Wei; Wang, Mian; Fu, Yebo; Castro, Nathan J; Fu, Sidney W; Zhang, Lijie Grace

2015-03-01

Traditional breast cancer (BrCa) bone metastasis models contain many limitations with regards to controllability, reproducibility and flexibility of design. In this study, a novel biomimetic bone microenvironment was created by integrating hydroxyapatite (HA) and native bioactive factors deposited by osteogenic induction of human bone marrow mesenchymal stem cells (MSCs) within a cytocompatible chitosan hydrogel. It was found that a 10% nanocrystalline HA (nHA) chitosan scaffold exhibited the highest BrCa adhesion and proliferation when compared to chitosan scaffolds with 20% nHA, 10% and 20% microcrystalline HA as well as amorphous HA. This 3-D tunable bone scaffold can provide a biologically relevant environment, increase cell-cell and cell-matrix interactions as found in native bone, and retain the behavior of BrCa cells with different metastasis potential (i.e. highly metastatic MDA-MB-231, less metastatic MCF-7 and transfected MDA-MB-231). The co-culture of MSCs and MDA-MB-231 in this bone model illustrated that MSCs have the capacity to upregulate the expression of the well-known metastasis-associated gene metadherin within BrCa cells. In summary, this study illustrates the ability of our 3-D bone model to create a biomimetic environment conducive to recapitulating the behavior of metastatic BrCa cells, making it a promising tool for in vitro BrCa cell bone metastasis study and for the discovery of potential therapeutics. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A cognitive movement scientist's view on the link between thought and action: insights from the "Badische Zimmer" metaphor.

PubMed

Hossner, Ernst-Joachim

2009-01-01

The problem of a bidirectional link between thought and action is approached from the perspective of cognitive movement science. The metaphor of the "Badische Zimmer" - an adaptation of Searle's Chinese room metaphor - is used to illustrate shortcomings in the classical conception of linear information processing and to introduce some features which current theories of movement control and learning should embrace. On this basis, the case is made for a return to an ideomotor view of motor control and learning based on effect prediction (E') as a function of the situational context (S') and one's own motor responses (R'). The relevance of the derived concept of sensorimotor chains linking elementary S'R'E' units in the course of motor learning is finally discussed with respect to potential implications for an integrative theory of perception, action, and decision making.

Initial tension loss in cerclage cables.

PubMed

Ménard, Jérémie; Émard, Maxime; Canet, Fanny; Brailovski, Vladimir; Petit, Yvan; Laflamme, George Y

2013-10-01

Cerclage cables, frequently used in the management of fractures and osteotomies, are associated with a high failure rate and significant loosening during surgery. This study compared the capacity to maintain tension of different types of orthopaedic cable systems. Multifilament Cobalt-Chrome (CoCr) cables with four different crimp/clamp devices (DePuy, Stryker, Zimmer and Smith&Nephew) and one non-metallic Nylon (Ny) cable from Kinamed were instrumented with a load cell to measure tension during insertion. Significant tension loss was observed with crimping for all cables (P<0.05). Removing the tensioner led to an additional unexpected tension loss (CoCr-DePuy: 18%, CoCr-Stryker: 29%, CoCr-Smith&Nephew: 33%, Ny: 46%, and CoCr-Zimmer: 52%). The simple CoCr (DePuy) cable system outperformed the more sophisticated locking devices due to its significantly better ability to prevent tension loss. Copyright © 2013 Elsevier Inc. All rights reserved.

Production process of a new cellulosic fiber with antimicrobial properties.

PubMed

Zikeli, Stefan

2006-01-01

The Lyocell process (system: cellulose-water-N-methylmorpholine oxide) of Zimmer AG offers special advantages for the production of cellulose fibers. The process excels by dissolving the most diverse cellulose types as these are optimally adjusted to the process by applying different pretreatment methods. Based on this stable process, Zimmer AG's objective is to impart to the Lyocell fiber additional value to improve quality of life and thus to tap new markets for the product. Thanks to the specific incorporation of seaweed, the process allows to produce cellulose Lyocell fibers with additional and new features. They are activated in a further step - by specific charging with metal ions - in order to obtain antibacterial properties. The favorable textile properties of fibers produced by the Lyocell process are not adversely affected by the incorporation of seaweed material or by activation to obtain an antibacterial fiber so that current textile products can be made from the fibers thus produced. The antibacterial effect is achieved by metal ion activation of the Lyocell fibers with incorporated seaweed, which contrasts with the antibacterial fibers known so far. Antibacterial fibers produced by conventional methods are in part only surface finished with antibacterially active chemicals or else they are produced by incorporating organic substances with antibacterial and fungicidal effects. Being made from cellulose, the antibacterial Lyocell fiber Sea Cell Active as the basis for quality textiles exhibits a special wear comfort compared to synthetic fibers with antibacterial properties and effects. This justifies the conclusion that the Zimmer Lyocell process provides genuine value added and that it is a springboard for further applications.

A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation.

PubMed

Ballios, Brian G; Cooke, Michael J; Donaldson, Laura; Coles, Brenda L K; Morshead, Cindi M; van der Kooy, Derek; Shoichet, Molly S

2015-06-09

The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC) and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC)-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs). The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Secretary Chu visits Argonne—Groundbreaking ceremony for new Energy Sciences building

ScienceCinema

Isaacs, Eric; Zimmer, Robert; Durbin, Dick; Chu, S

2018-06-06

U.S. Department of Energy Secretary Steven Chu, joined Senator Richard Durbin, University of Chicago President Robert Zimmer and Argonne Director Eric Isaacs to break ground for Argonne's new Energy and Sciences building.

77 FR 68103 - Foreign-Trade Zone 163-Ponce, PR; Notification of Proposed Production Activity; Zimmer...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-15

..., rods, angles shapes and sections of stainless steel; articles of iron or steel; and, artificial joints... information, contact Elizabeth Whiteman at [email protected] or (202) 482-0473. Dated: November 5...

Production development and utilization of Zimmer Station wet FGD by-products. Final report. Volume 5, A laboratory greenhouse study conducted in fulfillment of Phase 2, Objective 2 titled. Use of FGD by-product gypsum enriched with magnesium hydroxide as a soil amendment

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

Yibirin, H.; Stehouwer, R. C.; Bigham, J. M.

The Clean Air Act, as revised in 1992, has spurred the development of flue gas desulfurization (FGD) technologies that have resulted in large volumes of wet scrubber sludges. In general, these sludges must be dewatered, chemically treated, and disposed of in landfills. Disposal is an expensive and environmentally questionable process for which suitable alternatives must be found. Wet scrubbing with magnesium (Mg)-enhanced lime has emerged as an efficient, cost effective technology for SO 2 removal. When combined with an appropriate oxidation system, the wet scrubber sludge can be used to produce gypsum (CaSO 4-2H 2O) and magnesium hydroxide [Mg(OH) 2]more » of sufficient purity for beneficial re-use. Product value generally increases with purity of the by-product(s). The pilot plant at the CINERGY Zimmer Station near Cincinnati produces gypsum by products that can be formulated to contain varying amounts of Mg(OH) 2. Such materials may have agricultural value as soil conditioners, liming agents and sources of plant nutrients (Ca, Mg, S). This report describes a greenhouse study designed to evaluate by-product gypsum and Mg gypsum from the Zimmer Station pilot plant as amendments for improving the quality of agricultural soils and mine spoils that are currently unproductive because of phytotoxic conditions related to acidity and high levels of toxic dissolved aluminum (Al). In particular, the technical literature contains evidence to suggest that gypsum may be more effective than agricultural limestone in modifying soil chemical conditions below the immediate zone of application. Representative samples of by-product gypsum and Mg(OH) 2 from the Zimmer Station were initially characterized. The gypsum was of high chemical purity and consisted of well crystalline, lath-shaped particles of low specific surface area. By contrast, the by-product Mg(OH) 2 was a high surface area material (50 m 2 g -1) that contained 20% CaSO 4 with variable hydration state. Artificial blends of these materials containing 4% and 8% Mg(OH) 2 were prepared for comparison with other liming agents in the form of agricultural limestone and gypsum amended with laboratory Ca(OH) 2.« less

Development of laminated fiber-reinforced nanocomposites for bone regeneration

NASA Astrophysics Data System (ADS)

Xu, Weijie

There have been numerous efforts to develop synthetic and/or natural tissue engineering scaffolds that are suitable for bone regeneration applications to replace autograft and allograft bones. Current biomaterials as a scaffold for bone regeneration are limited by the extent of degradation concurrent with bone formation, mechanical strength, and the extent of osteogenic differentiation of marrow stromal cells migrating from the surrounding tissues. In this project, a novel laminated nanocomposite scaffold is fabricated, consisting of poly (L-lactide ethylene oxide fumarate) (PLEOF) hydrogel reinforced with poly (L-lactic acid) (PLLA) electrospun nanofibers and hydroxyapatite (HA) nanoparticles. PLEOF is a novel in situ crosslinkable macromer synthesized from biocompatible building units which can be functionalized with bioactive peptides like the cell-adhesive Arg--Gly--Asp (RGD) amino acid sequence. The hydrophilicity and degradation rate of the macromer can be tailored to a particular application by controlling the ratio of PEG to PLA blocks in the macromer and the unsaturated fumarate units can be used for in-situ crosslinking. The PLLA nanofibers were electrospun from high molecular weight PLLA. The laminated nanocomposites were fabricated by dry-hand lay up technique followed by compression molding and thermal crosslinking. The laminated nanocomposites were evaluated with respect to degradation, water uptake, mechanical strength, and the extent of osteogenic differentiation of bone marrow stromal (BMS) cells. Laminates with or without HA nanoparticles showed modulus values much higher than that of trabecular bone (50-100 MPa). The effect of laminated nanocomposites on osteogenic differentiation of BMS cells was determined in terms of cell number, ALPase activity and calcium content. Our results demonstrate that grafting RGD peptide and HA nanoparticles to a PLEOF hydrogel reinforced with PLLA nanofibers synergistically enhance osteogenic differentiation of BMS cells. In conclusion, the laminated nanocomposite with controllable degradation characteristics and robust mechanical properties is attractive as a synthetic bone-mimetic matrix for skeletal tissue regeneration.

Effect of Transplanting Various Concentrations of a Composite of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel on Articular Cartilage Repair in a Rabbit Model

PubMed Central

Ha, Chul-Won; Kim, Jin-A; Rhim, Ji-Heon; Park, Yong-Geun; Chung, Jun Young; Lee, Han-Jun

2016-01-01

Background Mesenchymal stem cells (MSCs) are known to have therapeutic potential for cartilage repair. However, the optimal concentration of MSCs for cartilage repair remains unclear. Therefore, we aimed to explore the feasibility of cartilage repair by human umbilical cord blood-derived MSCs (hUCB-MSCs) and to determine the optimal concentrations of the MSCs in a rabbit model. Methods Osteochondral defects were created in the trochlear groove of femur in 55 rabbits. Four experimental groups (11 rabbits/group) were treated by transplanting the composite of hUCB-MSCs and HA with various MSCs concentrations (0.1, 0.5, 1.0, and 1.5 x 107 cells/ml). One control group was left untreated. At 4, 8, and 16 weeks post-transplantation, the degree of cartilage repair was evaluated grossly and histologically. Findings Overall, transplanting hUCB-MSCs and HA hydrogel resulted in cartilage repair tissue with better quality than the control without transplantation (P = 0.015 in 0.1, P = 0.004 in 0.5, P = 0.004 in 1.0, P = 0.132 in 1.5 x 107 cells/ml). Interestingly, high cell concentration of hUCB-MSCs (1.5×107 cells/ml) was inferior to low cell concentrations (0.1, 0.5, and 1.0 x 107 cells/ml) in cartilage repair (P = 0.394,P = 0.041, P = 0.699, respectively). The 0.5 x 107 cells/ml group showed the highest cartilage repair score at 4, 8 and 16 weeks post transplantation, and followed by 0.1x107 cells/ml group or 1.0 x 107 cell/ml group. Conclusions The results of this study suggest that transplantation of the composite of hUCB-MSCs and HA is beneficial for cartilage repair. In addition, this study shows that optimal MSC concentration needs to be determined for better cartilage repair. PMID:27824874

Effect of Transplanting Various Concentrations of a Composite of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel on Articular Cartilage Repair in a Rabbit Model.

PubMed

Park, Yong-Beom; Ha, Chul-Won; Kim, Jin-A; Rhim, Ji-Heon; Park, Yong-Geun; Chung, Jun Young; Lee, Han-Jun

2016-01-01

Mesenchymal stem cells (MSCs) are known to have therapeutic potential for cartilage repair. However, the optimal concentration of MSCs for cartilage repair remains unclear. Therefore, we aimed to explore the feasibility of cartilage repair by human umbilical cord blood-derived MSCs (hUCB-MSCs) and to determine the optimal concentrations of the MSCs in a rabbit model. Osteochondral defects were created in the trochlear groove of femur in 55 rabbits. Four experimental groups (11 rabbits/group) were treated by transplanting the composite of hUCB-MSCs and HA with various MSCs concentrations (0.1, 0.5, 1.0, and 1.5 x 107 cells/ml). One control group was left untreated. At 4, 8, and 16 weeks post-transplantation, the degree of cartilage repair was evaluated grossly and histologically. Overall, transplanting hUCB-MSCs and HA hydrogel resulted in cartilage repair tissue with better quality than the control without transplantation (P = 0.015 in 0.1, P = 0.004 in 0.5, P = 0.004 in 1.0, P = 0.132 in 1.5 x 107 cells/ml). Interestingly, high cell concentration of hUCB-MSCs (1.5×107 cells/ml) was inferior to low cell concentrations (0.1, 0.5, and 1.0 x 107 cells/ml) in cartilage repair (P = 0.394,P = 0.041, P = 0.699, respectively). The 0.5 x 107 cells/ml group showed the highest cartilage repair score at 4, 8 and 16 weeks post transplantation, and followed by 0.1x107 cells/ml group or 1.0 x 107 cell/ml group. The results of this study suggest that transplantation of the composite of hUCB-MSCs and HA is beneficial for cartilage repair. In addition, this study shows that optimal MSC concentration needs to be determined for better cartilage repair.

Co-delivery of a laminin-111 supplemented hyaluronic acid based hydrogel with minced muscle graft in the treatment of volumetric muscle loss injury

PubMed Central

Goldman, Stephen M.; Henderson, Beth E. P.; Walters, Thomas J.

2018-01-01

Minced muscle autografting mediates de novo myofiber regeneration and promotes partial recovery of neuromuscular strength after volumetric muscle loss injury (VML). A major limitation of this approach is the availability of sufficient donor tissue for the treatment of relatively large VMLs without inducing donor site morbidity. This study evaluated a laminin-111 supplemented hyaluronic acid based hydrogel (HA+LMN) as a putative myoconductive scaffolding to be co-delivered with minced muscle grafts. In a rat tibialis anterior muscle VML model, delivery of a reduced dose of minced muscle graft (50% of VML defect) within HA+LMN resulted in a 42% improvement of peak tetanic torque production over unrepaired VML affected limbs. However, the improvement in strength was not improved compared to a 50% minced graft-only control group. Moreover, histological analysis revealed that the improvement in in vivo functional capacity mediated by minced grafts in HA+LMN was not accompanied by a particularly robust graft mediated regenerative response as determined through donor cell tracking of the GFP+ grafting material. Characterization of the spatial distribution and density of macrophage and satellite cell populations indicated that the combination therapy damps the heightened macrophage response while re-establishing satellite content 14 days after VML to a level consistent with an endogenously healing ischemia-reperfusion induced muscle injury. Moreover, regional analysis revealed that the combination therapy increased satellite cell density mostly in the remaining musculature, as opposed to the defect area. Based on the results, the following salient conclusions were drawn: 1) functional recovery mediated by the combination therapy is likely due to a superposition of de novo muscle fiber regeneration and augmented repair of muscle fibers within the remaining musculature, and 2) The capacity for VML therapies to augment regeneration and repair within the remaining musculature may have significant clinical impact and warrants further exploration. PMID:29329332

Biocompatibility Assessment of Novel Collagen-Sericin Scaffolds Improved with Hyaluronic Acid and Chondroitin Sulfate for Cartilage Regeneration

PubMed Central

Gălăţeanu, Bianca; Albu, Mădălina

2013-01-01

Cartilage tissue engineering (CTE) applications are focused towards the use of implantable biohybrids consisting of biodegradable scaffolds combined with in vitro cultured cells. Hyaluronic acid (HA) and chondroitin sulfate (CS) were identified as the most potent prochondrogenic factors used to design new biomaterials for CTE, while human adipose-derived stem cells (ASCs) were proved to display high chondrogenic potential. In this context, our aim was not only to build novel 3D porous scaffolds based on natural compounds but also to evaluate their in vitro biological performances. Therefore, for prospective CTE, collagen-sericin (Coll-SS) scaffolds improved with HA (5% or 10%) and CS (5% or 10%) were used as temporary physical supports for ASCs and were analyzed in terms of structural, thermal, morphological, and swelling properties and cytotoxic potential. To complete biocompatibility data, ASCs viability and proliferation potential were also assessed. Our studies revealed that Coll-SS hydrogels improved with 10% HA and 5% CS displayed the best biological performances in terms of cell viability, proliferation, morphology, and distribution. Thus, further work will address a novel 3D system including both HA 10% and CS 5% glycoproteins, which will probably be exposed to prochondrogenic conditions in order to assess its potential use in CTE applications. PMID:24308001

Preparation and in vitro characterization of thermosensitive and mucoadhesive hydrogels for nasal delivery of phenylephrine hydrochloride.

PubMed

Xu, Xiaofeng; Shen, Yan; Wang, Wei; Sun, Chunmeng; Li, Chang; Xiong, Yerong; Tu, Jiasheng

2014-11-01

The aim of the present work was to develop a nasal delivery system of phenylephrine hydrochloride (PE) in spray form to make prolonged remedy of nasal congestion. The formulations contain the thermosensitive hydrogel, i.e., Poloxamer 407 (P407) and Poloxamer 188 (P188) mixtures, and mucoadhesives, i.e., ε-polylysine (ε-PL) and low molecular weight sodium hyaluronate (MW 11,000Da). The in vitro characterizations of formulations including rheology studies, texture profiles and in vitro mucoadhesion potential were investigated after gelation temperatures measurements. The results showed that the concentration of P407 or P188 had significant influence on gelation temperature and texture profiles. The addition of mucoadhesives, though lowered the gel strength of formulations, increased interaction with mucin. After screening, two formulations (i.e., 1.0% PE/0.5% ε-PL/17% P407/0.5% P188 or Formulation A; and 1.0% PE/0.5% HA/17% P407/0.8% P188 or Formulation B) presenting suitable gelation temperatures (∼32°C) were used for further studies on in vitro release behaviors and mucosa ciliotoxicity. Both formulations showed sustained release of PE for up to 8h and similar toxicity to saline, the negative control. Thus, the thermosensitive and mucoadhesive PE-containing hydrogels are promising to achieve prolonged decongestion in nasal cavity. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed Central

Heris, Hossein K.; Rahmat, Meysam

2015-01-01

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

Optimization and translation of MSC-based hyaluronic acid hydrogels for cartilage repair

NASA Astrophysics Data System (ADS)

Erickson, Isaac E.

2011-12-01

Traumatic injury and disease disrupt the ability of cartilage to carry joint stresses and, without an innate regenerative response, often lead to degenerative changes towards the premature development of osteoarthritis. Surgical interventions have yet to restore long-term mechanical function. Towards this end, tissue engineering has been explored for the de novo formation of engineered cartilage as a biologic approach to cartilage repair. Research utilizing autologous chondrocytes has been promising, but clinical limitations in their yield have motivated research into the potential of mesenchymal stem cells (MSCs) as an alternative cell source. MSCs are multipotent cells that can differentiate towards a chondrocyte phenotype in a number of biomaterials, but no combination has successfully recapitulated the native mechanical function of healthy articular cartilage. The broad objective of this thesis was to establish an MSC-based tissue engineering approach worthy of clinical translation. Hydrogels are a common class of biomaterial used for cartilage tissue engineering and our initial work demonstrated the potential of a photo-polymerizable hyaluronic acid (HA) hydrogel to promote MSC chondrogenesis and improved construct maturation by optimizing macromer and MSC seeding density. The beneficial effects of dynamic compressive loading, high MSC density, and continuous mixing (orbital shaker) resulted in equilibrium modulus values over 1 MPa, well in range of native tissue. While compressive properties are crucial, clinical translation also demands that constructs stably integrate within a defect. We utilized a push-out testing modality to assess the in vitro integration of HA constructs within artificial cartilage defects. We established the necessity for in vitro pre-maturation of constructs before repair to achieve greater integration strength and compressive properties in situ. Combining high MSC density and gentle mixing resulted in integration strength over 500 kPa, nearly 10-fold greater than previous reports of integration with MSC-based constructs. Furthermore, we demonstrated the durability of this repair system by applying dynamic loading and showed its functional contribution to the distribution of compressive loads across the repair space. Overall, the studies contained within this thesis offer the first MSC-based tissue engineering strategy that successfully recapitulates native mechanical function while also demonstrating the potential for complete functional cartilage repair.

Chondrogenically primed tonsil-derived mesenchymal stem cells encapsulated in riboflavin-induced photocrosslinking collagen-hyaluronic acid hydrogel for meniscus tissue repairs.

PubMed

Koh, Rachel H; Jin, Yinji; Kang, Byung-Jae; Hwang, Nathaniel S

2017-04-15

Current meniscus tissue repairing strategies involve partial or total meniscectomy, followed by allograft transplantation or synthetic material implantation. However, allografts and synthetic implants have major drawbacks such as the limited supply of grafts and lack of integration into host tissue, respectively. In this study, we investigated the effects of conditioned medium (CM) from meniscal fibrochondrocytes and TGF-β3 on tonsil-derived mesenchymal stem cells (T-MSCs) for meniscus tissue engineering. CM-expanded T-MSCs were encapsulated in riboflavin-induced photocrosslinked collagen-hyaluronic acid (COL-RF-HA) hydrogels and cultured in chondrogenic medium containing TGF-β3. In vitro results indicate that CM-expanded cells followed by TGF-β3 exposure stimulated the expression of fibrocartilage-related genes (COL2, SOX9, ACAN, COL1) and production of extracellular matrix components. Histological assessment of in vitro and subcutaneously implanted in vivo constructs demonstrated that CM-expanded cells followed by TGF-β3 exposure resulted in highest cell proliferation, GAG accumulation, and collagen deposition. Furthermore, when implanted into meniscus defect model, CM treatment amplified the potential of TGF-β3 and induced complete regeneration. Conditioned medium derived from chondrocytes have been reported to effectively prime mesenchymal stem cells toward chondrogenic lineage. Type I collagen is the main component of meniscus extracellular matrix and hyaluronic acid is known to promote meniscus regeneration. In this manuscript, we investigated the effects of conditioned medium (CM) and transforming growth factor-β3 (TGF-β3) on tonsil-derived mesenchymal stem cells (T-MSCs) encapsulated in riboflavin-induced photocrosslinked collagen-hyaluronic acid (COL-RF-HA) hydrogel. We employed a novel source of conditioned medium, derived from meniscal fibrochondrocytes. Our in vitro and in vivo results collectively illustrate that CM-expanded cells followed by TGF-β3 exposure have the best potential for meniscus regeneration. This manuscript highlights a novel stem cell commitment strategy combined with biomaterials designs for meniscus regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Study of the cell activity in three-dimensional cell culture by using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Arunngam, Pakajiraporn; Mahardika, Anggara; Hiroko, Matsuyoshi; Andriana, Bibin Bintang; Tabata, Yasuhiko; Sato, Hidetoshi

2018-02-01

The purpose of this study is to develop a estimation technique of local cell activity in cultured 3D cell aggregate with gelatin hydrogel microspheres by using Raman spectroscopy. It is an invaluable technique allowing real-time, nondestructive, and invasive measurement. Cells in body generally exist in 3D structure, which physiological cell-cell interaction enhances cell survival and biological functions. Although a 3D cell aggregate is a good model of the cells in living tissues, it was difficult to estimate their physiological conditions because there is no effective technique to make observation of intact cells in the 3D structure. In this study, cell aggregates were formed by MC3T-E1 (pre-osteoblast) cells and gelatin hydrogel microspheres. In appropriate condition MC3T-E1 cells can differentiate into osteoblast. We assume that the activity of the cell would be different according to the location in the aggregate because the cells near the surface of the aggregate have more access to oxygen and nutrient. Raman imaging technique was applied to measure 3D image of the aggregate. The concentration of the hydroxyapatite (HA) is generated by osteoblast was estimated with a strong band at 950-970 cm-1 which assigned to PO43- in HA. It reflects an activity of the specific site in the cell aggregate. The cell density in this specific site was analyzed by multivariate analysis of the 3D Raman image. Hence, the ratio between intensity and cell density in the site represents the cell activity.

Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds

NASA Astrophysics Data System (ADS)

Castro, Nathan J.; O'Brien, Joseph; Zhang, Lijie Grace

2015-08-01

The osteochondral interface of an arthritic joint is notoriously difficult to regenerate due to its extremely poor regenerative capacity and complex stratified architecture. Native osteochondral tissue extracellular matrix is composed of numerous nanoscale organic and inorganic constituents. Although various tissue engineering strategies exist in addressing osteochondral defects, limitations persist with regards to tissue scaffolding which exhibit biomimetic cues at the nano to micro scale. In an effort to address this, the current work focused on 3D printing biomimetic nanocomposite scaffolds for improved osteochondral tissue regeneration. For this purpose, two biologically-inspired nanomaterials have been synthesized consisting of (1) osteoconductive nanocrystalline hydroxyapatite (nHA) (primary inorganic component of bone) and (2) core-shell poly(lactic-co-glycolic) acid (PLGA) nanospheres encapsulated with chondrogenic transforming growth-factor β1 (TGF-β1) for sustained delivery. Then, a novel table-top stereolithography 3D printer and the nano-ink (i.e., nHA + nanosphere + hydrogel) were employed to fabricate a porous and highly interconnected osteochondral scaffold with hierarchical nano-to-micro structure and spatiotemporal bioactive factor gradients. Our results showed that human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation were greatly improved in the biomimetic graded 3D printed osteochondral construct in vitro. The current work served to illustrate the efficacy of the nano-ink and current 3D printing technology for efficient fabrication of a novel nanocomposite hydrogel scaffold. In addition, tissue-specific growth factors illustrated a synergistic effect leading to increased cell adhesion and directed stem cell differentiation.

Keynote Presentation: Genome Beat (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

ScienceCinema

Zimmer, Carl [New York Times, New York, NY (United States)

2018-05-23

Carl Zimmer, a reporter for the New York Times, speaks on "The Genome Beat," the opening keynote presentation at the JGI User 7th Annual Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, California.

Keynote Presentation: Genome Beat (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

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

Zimmer, Carl

Carl Zimmer, a reporter for the New York Times, speaks on "The Genome Beat," the opening keynote presentation at the JGI User 7th Annual Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, California.

Rogers, Lazarus, and Shostrom in Content Analysis.

ERIC Educational Resources Information Center

O'Dell, Jerry W.; Bahmer, Alma J.

1981-01-01

Subjected Shostrom's films of Rogers, Lazarus, and Shostrom working with a patient to a content analysis using the system developed by Zimmer and Cowles. Differences in verbal activity on the part of therapist and patient were noted, appearing consistent with the principles of the various therapies. (Author)

Novel bio-synthetic hybrid materials and coculture systems for musculoskeletal tissue engineering

NASA Astrophysics Data System (ADS)

Lee, Hyeseung Janice

Tissue Engineering is a truly exciting field of this age, trying to regenerate and repair impaired tissues. Unlike the old artificial implants, tissue engineering aims at making a long-term functional biological replacement. One strategy for such tissue engineering requires the following three components: cells, scaffolds, and soluble factors. Cells are cultured in a three-dimensional (3D) scaffold with medium containing various soluble factors. Once a tissue is developed in vitro, then it is implanted in vivo. The overall goal of this thesis was to develop novel bio-synthetic hybrid scaffolds and coculture system for musculoskeletal tissue engineering. The most abundant cartilage extracellular matrix (ECM) components are collagen and glycosaminoglycan (GAG), which are the natural scaffold for chondrocytes. As two different peptides, collagen mimetic peptide (CMP) and hyaluronic acid binding peptide (HABPep) were previously shown to bind to collagen and hyaluronic acid (HA) of GAG, respectively, it was hypothesized that immobilizing CMP and HABP on 3D scaffold would results in an interaction between ECM components and synthetic scaffolds via peptide-ECM bindings. CMP or HABPep-conjugated photopolymerizable poly(ethylene oxide) diacrylate (PEODA) hydrogels were synthesized and shown to retain encapsulated collagen or HA, respectively. This result supported that conjugated CMP and HABPep can interact with collagen and HA, respectively, and can serve as biological linkers in 3D synthetic hydrogels. When chondrocytes or mesenchymal stem cells (MSCs) were seeded, cells in CMP-conjugated scaffolds produced significantly more amount of type II collagen and GAG, compared to those in control scaffolds. Moreover, MSCs cultured in CMP-conjugated scaffolds exhibited lower level of hypertrophic markers, cbfa-1 and type X collagen. These results demonstrated that enhanced interaction between collagen and scaffold via CMP improves chondrogenesis of chondrocytes and MSCs and further reduces hypertrophy of differentiating MSCs. On the other hand, although cells in HABPep-conjugated scaffolds produced less ECM components, they survived and proliferated significantly more than those in control, resulting in overall increase in ECM contents per scaffold. Once implanted in vivo, HABPep-conjugated constructs increased GAG and type II collagen contents further, compared to those of the control hydrogel. These results showed that enhanced interaction between HA and scaffold via HABPep improved the in vitro culture expansion of MSCs and further ECM production in vivo. Effects of cell-secreted bioactive factors via cell-cell communication on stem cell differentiation were also investigated in 3D bilayer system. First, when mesenchymal progenitor cells (MPCs) were cocultured with ES-derived cells (ESDC), morphogenetic factors secreted by ESDCs showed a potential to improve MPC chondrogenesis in both control and chondrogenic medium by increasing not only MPC's chondrogenic gene expression, but also ECM production. Moreover, the effect of ESDC cell-mediated chondrogenesis of MSC could not be mimicked by chondrogenic medium supplemented with TGF-beta1 and dexamethasone. Secondly, coculturing hepatic cells enhanced specific chondrogenic differentiation of ES cells in the 3D bilayer system. These studies demonstrated that cell-secreted soluble factors can be used to guide stem cell differentiation.

Biocompatibility of hyaluronic acid hydrogels prepared by porous hyaluronic acid microbeads

NASA Astrophysics Data System (ADS)

Kim, Jin-Tae; Lee, Deuk Yong; Kim, Tae-Hyung; Song, Yo-Seung; Cho, Nam-Ihn

2014-05-01

Hyaluronic acid hydrogels (HAHs) were synthesized by immersing HA microbeads crosslinked with divinyl sulfone in a phosphate buffered saline solution to evaluate the biocompatibility of the gels by means of cytotoxicity, genotoxicity ( in vitro chromosome aberration test, reverse mutation assay, and in vivo micronucleus test), skin sensitization, and intradermal reactivity. The HAHs induced no cytotoxicity or genotoxicity. In guinea pigs treated with grafts and prostheses, no animals died and there were no abnormal clinical signs. The sensitization scores were zero in all guinea pigs after 24 h and 48 h challenge, suggesting that the HAHs had no contact allergic sensitization in the guinea pig maximization test. No abnormal signs were found in New Zealand White rabbits during the 72 h observation period after the injection. There was no difference between the HAHs and negative control mean scores because skin reaction such as erythema or oedema was not observed after injection. Experimental results suggest that the HAHs would be suitable for soft tissue augmentation due to the absence of cytotoxicity, genotoxicity, skin sensitization, and intradermal reactivity.

Hydroxyethyl methacrylate grafted carboxy methyl tamarind (CMT-g-HEMA) polysaccharide based matrix as a suitable scaffold for skin tissue engineering.

PubMed

Choudhury, Priyanka; Kumar, Satish; Singh, Abhishek; Kumar, Ashutosh; Kaur, Navneet; Sanyasi, Sridhar; Chawla, Saurabh; Goswami, Chandan; Goswami, Luna

2018-06-01

Patho-physiologies related to skin are diverse in nature such as burns, skin ulcers, atopic dermatitis, psoriasis etc. which impose severe bio-medical problems and thus enforce requirement of new and healthy skin prepared through tissues engineering methodologies. However, fully functional and biodegradable matrix for attachment, growth, proliferation and differentiation of the relevant cells is not available. In the present study, we introduce a set of hydrogels synthesized by incorporation of a synthetic monomer (Hydroxyethlmethacryate) with a semi-synthetic polymer backbone (carboxy methyl tamarind, CMT) in different mole ratios. We termed these materials as CMT:HEMA based hydrogels and these were characterized by different physico-chemical techniques, namely by X-Ray Diffraction, SEM and Dynamic Light Scattering. Biocompatibility studies with HaCaT, NIH-3T3 and mouse dermal fibroblasts confirm that this material is biocompatible. MTT assay further confirmed that this material does not have any cytotoxic effects. Assays for mitochondrial functionality such as ATP assay and mitochondrial reactive oxygen (ROS) generation also suggest that this material is safe and does not have any cytotoxicity. Hemolytic assay with red blood cells and acute skin irritation test on SD Rats confirmed that this material is suitable for ex-vivo application in future. We suggest that this hydrogel is suitable for in-vivo applications and may have clinical and commercial importance against skin disorders. Copyright © 2018. Published by Elsevier Ltd.

Vibration stimulates vocal mucosa-like matrix expression by hydrogel-encapsulated fibroblasts.

PubMed

Kutty, Jaishankar K; Webb, Ken

2010-01-01

The composition and organization of the vocal fold extracellular matrix (ECM) provide the viscoelastic mechanical properties that are required to sustain high-frequency vibration during voice production. Although vocal injury and pathology are known to produce alterations in matrix physiology, the mechanisms responsible for the development and maintenance of vocal fold ECM are poorly understood. The objective of this study was to investigate the effect of physiologically relevant vibratory stimulation on ECM gene expression and synthesis by fibroblasts encapsulated within hyaluronic acid hydrogels that approximate the viscoelastic properties of vocal mucosa. Relative to static controls, samples exposed to vibration exhibited significant increases in mRNA expression levels of HA synthase 2, decorin, fibromodulin and MMP-1, while collagen and elastin expression were relatively unchanged. Expression levels exhibited a temporal response, with maximum increases observed after 3 and 5 days of vibratory stimulation and significant downregulation observed at 10 days. Quantitative assays of matrix accumulation confirmed significant increases in sulphated glycosaminoglycans and significant decreases in collagen after 5 and 10 days of vibratory culture, relative to static controls. Cellular remodelling and hydrogel viscosity were affected by vibratory stimulation and were influenced by varying the encapsulated cell density. These results indicate that vibration is a critical epigenetic factor regulating vocal fold ECM and suggest that rapid restoration of the phonatory microenvironment may provide a basis for reducing vocal scarring, restoring native matrix composition and improving vocal quality. 2009 John Wiley & Sons, Ltd.

Dimentions of Counselee Responses over Several Therapy Sessions

ERIC Educational Resources Information Center

Zimmer, Jules M.; And Others

1972-01-01

The results of the current study, as well as the Zimmer and Cowles (1972) study using quite different procedures, involved a comparison of client-centered, gestalt, and rational therapies and do not support the conclusion that therapeutic relationships tend to be characteristically the same. Theoretical orientation as operationalized by…

Law Related Education.

ERIC Educational Resources Information Center

Maslow, R., Ed.; Kirchgaessner, R., Ed.

1989-01-01

This journal edition focuses upon the many resources for teachers to draw upon in order to infuse law-related education (LRE) into their classrooms. Isidore Starr explains the reasons behind the LRE movement, while Mabel McKinney-Browning describes the existing American Bar Association's programs in LRE. Judith Zimmer covers the Street Law…

78 FR 1825 - Notice of Establishment of an Animal and Plant Health Inspection Service Stakeholder Registry

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-09

... CONTACT: Ms. Hallie Zimmers, Advisor for State and Stakeholder Relations, Legislative and Public Affairs... communication with our many and diverse stakeholders. To join the registry and receive messages, stakeholders... subscriptions may access the expanded registry at: https://public.govdelivery.com/accounts/USDAAPHIS/subscriber...

Understanding bactericidal performance on ambient light activated TiO2-InVO4 nanostructured films.

PubMed

He, Ziming; Xu, Qingchi; Tan, Timothy Thatt Yang

2011-12-01

TiO(2)-InVO(4) nanostructured films were coated onto glass substrates and systematically investigated for their bactericidal activities using Escherichia coli (E. coli) as the model bacterium under ambient light illumination. The uniform TiO(2)-InVO(4) nanostructured films were prepared using titanium isopropoxide (TTIP) as the precursor via a simple sol-gel approach. Polyethylenimine (PEI) was used as a surfactant to ensure uniform dispersion of InVO(4) and a sacrificial pore-inducing agent, generating nanostructured films. Compared to unmodified TiO(2) film, the current TiO(2)-InVO(4) films exhibited enhanced bactericidal activities under ambient light illumination. Bacterial cell "photo-fixation" was demonstrated to be crucial in enhancing the bactericidal activity. A bacterial-nanostructured surface interaction mechanism was proposed for the current ambient-light activated nanostructured film.

Microwave-induced biomimetic approach for hydroxyapatite coatings of chitosan scaffolds.

PubMed

Kaynak Bayrak, Gökçe; Demirtaş, T Tolga; Gümüşderelioğlu, Menemşe

2017-02-10

Simulated body fluid (SBF) can form calcium phosphates on osteoinductive materials, so it is widely used for coating of bone scaffolds to mimic natural extracellular matrix (ECM). However, difficulties of bulk coating in 3D scaffolds and the necessity of long process times are the common problems for coating with SBF. In the present study, a microwave-assisted process was developed for rapid and internal coating of chitosan scaffolds. The scaffolds were fabricated as superporous hydrogel (SPH) by combining microwave irradiation and gas foaming methods. Then, they were immersed into 10x  SBF-like solution and homogenous bone-like hydroxyapatite (HA) coating was achieved by microwave treatment at 600W without the need of any nucleating agent. Cell culture studies with MC3T3-E1 preosteoblasts showed that microwave-assisted biomimetic HA coating process could be evaluated as an efficient and rapid method to obtain composite scaffolds for bone tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

* Tissue-Specific Extracellular Matrix Enhances Skeletal Muscle Precursor Cell Expansion and Differentiation for Potential Application in Cell Therapy.

PubMed

Zhang, Deying; Zhang, Yong; Zhang, Yuanyuan; Yi, Hualin; Wang, Zhan; Wu, Rongpei; He, Dawei; Wei, Guanghui; Wei, Shicheng; Hu, Yun; Deng, Junhong; Criswell, Tracy; Yoo, James; Zhou, Yu; Atala, Anthony

2017-08-01

Skeletal muscle precursor cells (MPCs) are considered a key candidate for cell therapy in the treatment of skeletal muscle dysfunction due to injury, disease, or age. However, expansion of a sufficient number of functional skeletal muscle cells in vitro from a small tissue biopsy has been challenging due to changes in phenotypic expression of these cells under traditional culture conditions. Thus, the aim of the study was to develop a better culture system for the expansion and myo-differentiation of MPCs that could further be used for therapy. For this purpose, we developed an ideal method of tissue decellularization and compared the ability of different matrices to support MPC growth and differentiation. Porcine-derived skeletal muscle and liver and kidney extracellular matrix (ECM) were generated by decellularization methods consisting of distilled water, 0.2 mg/mL DNase, or 5% fetal bovine serum. Acellular matrices were further homogenized, dissolved, and combined with a hyaluronic acid-based hydrogel decorated with heparin (ECM-HA-HP). The cell proliferation and myogenic differentiation capacity of human MPCs were assessed when grown on gel alone, ECM, or each ECM-HA-HP substrate. Human MPC proliferation was significantly enhanced when cultured on the ECM-HA-HP substrates compared to the other substrates tested, with the greatest proliferation on the muscle ECM-HA-HP (mECM-HA-HP) substrate. The number of differentiated myotubes was significantly increased on the mECM-HA-HP substrate compared to the other gel-ECM substrates, as well as the numbers of MPCs expressing specific myogenic cell markers (i.e., myosin, desmin, myoD, and myf5). In conclusion, skeletal mECM-HA-HP as a culture substrate provided an optimal culture microenvironment potentially due to its similarity to the in vivo environment. These data suggest a potential use of skeletal muscle-derived ECM gel for the expansion and differentiation of human MPCs for cell-based therapy for skeletal muscle dysfunction.

From Article to Action: Fostering Literacy Skills for Diverse Learners across Learning Environments

ERIC Educational Resources Information Center

Meyer, Lori Erbrederis

2017-01-01

Kate Zimmer's article ("Enhancing Interactions With Children With Autism Through Storybook Reading: A Caregiver's Guide," v20 n3 p133-144 Sep 2017) encourages practitioners to provide information on effective instructional strategies that could increase positive interactions during shared book reading between children who have an autism…

Broadening the Definition of Engagement for Students with Severe Disabilities: A Phenomenological Study of the Experts in the Field

ERIC Educational Resources Information Center

Hollingshead, Aleksandra K.

2013-01-01

While a great deal has been written about the complexities of engagement for learners without severe disabilities, there is less for students with severe disabilities. Engagement as a complex construct, consisting of behavioral, cognitive, and emotional components (Finn & Zimmer, 2012; Fredricks, Blumenfeld, & Paris, 2004; Skinner &…

Getting Inside the Black Box: Examining How the Operation of Charter Schools Affects Performance

ERIC Educational Resources Information Center

Zimmer, Ron; Buddin, Richard

2007-01-01

In recent years, a series of articles have examined the performance of charter schools with mixed results. Some of this research has shown that charter school performance varies by charter type or the age of the school (Bifulco & Ladd, 2006; Buddin & Zimmer, 2005; Hanushek, Kain, & Rivkin, 2002; Sass, 2006). However, this research has…

Construction of 3D multicellular microfluidic chip for an in vitro skin model.

PubMed

Lee, Sojin; Jin, Seon-Pil; Kim, Yeon Kyung; Sung, Gun Yong; Chung, Jin Ho; Sung, Jong Hwan

2017-06-01

Current in vitro skin models do not recapitulate the complex architecture and functions of the skin tissue. In particular, on-chip construction of an in vitro model comprising the epidermis and dermis layer with vascular structure for mass transport has not been reported yet. In this study, we aim to develop a microfluidic, three-dimensional (3D) skin chip with fluidic channels using PDMS and hydrogels. Mass transport within the collagen hydrogel matrix was verified with fluorescent model molecules, and a transport-reaction model of oxygen and glucose inside the skin chip was developed to aid the design of the microfluidic skin chip. Comparison of viabilities of dermal fibroblasts and HaCaT cultured in the chip with various culture conditions revealed that the presence of flow plays a crucial role in maintaining the viability, and both cells were viable after 10 days of air exposure culture. Our 3D skin chip with vascular structures can be a valuable in vitro model for reproducing the interaction between different components of the skin tissue, and thus work as a more physiologically realistic platform for testing skin reaction to cosmetic products and drugs.

Model studies of diffusion-controlled (2-hydroxyethyl methacrylate) HEMA hydrogel membranes for controlled release of proteins

NASA Astrophysics Data System (ADS)

Appawu, Jennifer A. M.

This thesis project consisted of three main components that were connected by roots in chemical analysis for studies in tissue engineering. The first part focused on characterizing the structural parameters of synthetic cross-linked poly (2-hydroxyethyl methacrylate) (Poly(HEMA) hydrogel membranes to determine optimal formulations for clinical studies. Poly(HEMA) membranes were loaded with Keratincocyte Growth Factor (KGF) for controlled release studies. Protein loading and release kinetics were determined with fluorescence spectroscopy. The spatial distribution of a protein in the membrane was determined using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). The last part of the project focused on determining the biological effects of the polymer membranes in-vitro with a model cell line and a pilot in-vivo animal study. Based on the components completed in this project, five chapters are included in this dissertation document and are summarized below. A new protocol was developed using fluorescence spectroscopy that measured the rate of protein diffusion into cross-linked polymer membranes by measuring the change in the fluorescence intensity of the protein solution. This technique was also able to detect a conformational change that occurs within protein when KGF was imbibed within these cross-linked polymer membranes. ToF-SIMS chemical imaging and 3D depth profiling was used to determine the spatial distribution of KGF protein in frozen-hydrated HEMA hydrogel membranes. The 3D depth profiles showed that the KGF protein was aggregated in bright spots that indicated that KGF was not spatially homogenous on the surface and through the depth profiles. 3D depth profiles of the membranes studied at various times during release studies show that areas with aggregated proteins were retained during release, and at times with maximum release. The interpretation of the bright regions is that the KGf protein interacted with the cross-linked network of the hydrogel membranes, making it not available for release. The in-vitro biological experiments with the HaCaT cell line showed that the HEMA hydrogels were capable of sustaining cell viability, proliferation, and adhesion through cell adhesion and wounding experiments. The pilot in-vivo animal study also revealed that KGF protein had retained its pharmacological activity. The study also showed that the KGF protein enhanced the rate of wound closure.

An Evaluation method for C2 Cyber-Physical Systems Reliability Based on Deep Learning

DTIC Science & Technology

2014-06-01

the reliability testing data of the system, we obtain the prior distribution of the relia- bility is 1 1( ) ( ; , )R LG R r  . By Bayes theo- rem ...criticality cyber-physical sys- tems[C]//Proc of ICDCS. Piscataway, NJ: IEEE, 2010:169-178. [17] Zimmer C, Bhat B, Muller F, et al. Time-based intrusion de

Ubi Materia, Ibi Geometria

DTIC Science & Technology

2000-09-29

of the birth of new physics and astronomy , and as contribution to obscure rhetoric in speculative quantum physics texts. In fact, not only...Copernican system has to be valid (Myaterium Cosmographicum). (One might, however, with justification doubt that the system presented by Copernicus in his...Kepleri astronomi Opera Omnia, Vol. I. Editit Christian Frisch. Frankofurti a.M.-Erlangae, Heyder & Zimmer 1858-1871. (Johannes Kepler, Gesammelte Werke

Modeling of Habitat and Foraging Behavior of Beaked Whales in the Southern California Bight

DTIC Science & Technology

2013-09-30

signals of a beaked whale at Palmyra Atoll . J Acoust Soc Am 127:3790-3799 Johnson M, Madsen PT, Zimmer WMX, Aguilar de Soto N, Tyack P (2006) Foraging...Biol 208:181-194 McDonald MA, Hildebrand JA, Wiggins SM, Johnston DW, Polovina JJ (2009) An acoustic survey of beaked whales at Cross Seamount near

Joseph Campbell, Jung, Anne Tyler, and "The Cards": The Spiritual Journey in "Searching for Caleb."

ERIC Educational Resources Information Center

Thomson, Karen M.

Joseph Campbell, Carl Jung, and Anne Tyler have all dealt with spiritual journeys and card reading in their writings. In his book "Tarot Revelations," Joseph Campbell discusses his first association with tarot cards, dating from 1943, when he was introduced to the symoblism of playing cards by his friend and mentor, Heinrich Zimmer. Carl…

Comparison of robotic-assisted and conventional manual implantation of a primary total knee arthroplasty.

PubMed

Park, Sang Eun; Lee, Chun Taek

2007-10-01

This study was aimed to compare robotic-assisted implantation of a total knee arthroplasty with conventional manual implantation. We controlled, randomized, and reviewed 72 patients for total knee arthroplasty assigned to undergo either conventional manual implantation (excluding navigation-assisted implantation cases) of a Zimmer LPS prosthesis (Zimmer, Warsaw, Ind) (30 patients: group 1) or robotic-assisted implantation of such a prosthesis (32 patients: group 2). The femoral flexion angle (gamma angle) and tibial angle (delta angle) in the lateral x-ray of group 1 were 4.19 +/- 3.28 degrees and 89.7 +/- 1.7 degrees, and those of group 2 were 0.17 +/- 0.65 degrees and 85.5 +/- 0.92 degrees. The major complications were from improper small skin incision during a constraint attempt of minimally invasive surgery and during bulk fixation frame pins insertion. Robotic-assisted technology had definite advantages in terms of preoperative planning, accuracy of the intraoperative procedure, and postoperative follow-up, especially in the femoral flexion angle (gamma angle) and tibial flexion angle (delta angle) in the lateral x-ray, and in the femoral flexion angle (alpha angle) in the anteroposterior x-ray. But a disadvantage was the high complication rate in early stage.

Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology.

PubMed

Deegan, Daniel B; Zimmerman, Cynthia; Skardal, Aleksander; Atala, Anthony; Shupe, Thomas D

2015-03-01

Tissue engineering and cell based liver therapies have utilized primary hepatocytes with limited success due to the failure of hepatocytes to maintain their phenotype in vitro. In order to overcome this challenge, hyaluronic acid (HA) cell culture substrates were formulated to closely mimic the composition and stiffness of the normal liver cellular microenvironment. The stiffness of the substrate was modulated by adjusting HA hydrogel crosslinking. Additionally, the repertoire of bioactive molecules within the HA substrate was bolstered by supplementation with normal liver extracellular matrix (ECM). Primary human hepatocyte viability and phenotype were determined over a narrow physiologically relevant range of substrate stiffnesses from 600 to 4600Pa in both the presence and absence of liver ECM. Cell attachment, viability, and organization of the actin cytoskeleton improved with increased stiffness up to 4600Pa. These differences were not evident in earlier time points or substrates containing only HA. However, gene expression for the hepatocyte markers hepatocyte nuclear factor 4 alpha (HNF4α) and albumin significantly decreased on the 4600Pa stiffness at day 7 indicating that cells may not have maintained their phenotype long-term at this stiffness. Function, as measured by albumin secretion, varied with both stiffness and time in culture and peaked at day 7 at the 1200Pa stiffness, slightly below the stiffness of normal liver ECM at 3000Pa. Overall, gel stiffness affected primary human hepatocyte cell adhesion, functional marker expression, and morphological characteristics dependent on both the presence of liver ECM in gel substrates and time in culture. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ocular Safety of Topical Naltrexone

DTIC Science & Technology

2013-04-01

prescription medicines , vitamins and herbal supplements. Especially tell your doctor if you take any opioid-containing medicines for pain, cough, or...squamous cell carcinoma. International Journal of Molecular Medicine 2000;5:191-6. 13. Zagon IS, McLaughlin PJ. Naloxone prolongs the survival time of mice...human pancreatic adenocarcinoma. International Journal of Molecular Medicine 2000;5:77-84. 18 35. Zagon IS, Verderame MF, Zimmer WE, McLaughlin PJ

Accuracy of mechanical torque-limiting devices for dental implants.

PubMed

L'Homme-Langlois, Emilie; Yilmaz, Burak; Chien, Hua-Hong; McGlumphy, Edwin

2015-10-01

A common complication in implant dentistry is unintentional implant screw loosening. The critical factor in the prevention of screw loosening is the delivery of the appropriate target torque value. Mechanical torque-limiting devices (MTLDs) are the most frequently recommended devices by the implant manufacturers to deliver the target torque value to the screw. Two types of MTLDs are available: friction-style and spring-style. Limited information is available regarding the influence of device type on the accuracy of MTLDs. The purpose of this study was to determine and compare the accuracy of spring-style and friction-style MTLDs. Five MTLDs from 6 different dental implant manufacturers (Astra Tech/Dentsply, Zimmer Dental, Biohorizons, Biomet 3i, Straumann [ITI], and Nobel Biocare) (n=5 per manufacturer) were selected to determine their accuracy in delivering target torque values preset by their manufacturers. All torque-limiting devices were new and there were 3 manufacturers for the friction-style and 3 manufacturers for the spring-style. The procedure of target torque measurement was performed 10 times for each device and a digital torque gauge (Chatillon Model DFS2-R-ND; Ametek) was used to record the measurements. Statistical analysis used nonparametric tests to determine the accuracy of the MTLDs in delivering target torque values and Bonferroni post hoc tests were used to assess pairwise comparisons. Median absolute difference between delivered torque values and target torque values of friction-style and spring-style MTLDs were not significantly different (P>.05). Accuracy of Astra Tech and Zimmer Dental friction-style torque-limiting devices were significantly different than Biohorizons torque-limiting devices (P<.05). There is no difference between the accuracy of new friction-style MTLDs and new spring-style MTLDs. All MTLDs fell within ±10% of the target torque value. Astra Tech and Zimmer Dental friction-style torque-limiting devices were significantly more accurate than Biohorizons (C) torque-limiting devices (P<.05); however, all the torque-limiting devices fell within ±10% of the target torque value preset by the manufacturers. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Efficacy of a crosslinked hyaluronic acid-based hydrogel as a tear film supplement: a masked controlled study.

PubMed

Williams, David L; Mann, Brenda K

2014-01-01

Keratoconjunctivitis sicca (KCS), or dry eye, is a significant medical problem in both humans and dogs. Treating KCS often requires the daily application of more than one type of eye drop in order to both stimulate tear prodcution and provide a tear supplement to increase hydration and lubrication. A previous study demonstrated the potential for a crosslinked hyaluronic acid-based hydrogel (xCMHA-S) to reduce the clinical signs associated with KCS in dogs while using a reduced dosing regimen of only twice-daily administration. The present study extended those results by comparing the use of the xCMHA-S to a standard HA-containing tear supplement in a masked, randomized clinical study in dogs with a clinical diagnosis of KCS. The xCMHA-S was found to significantly improve ocular surface health (conjunctival hyperaemia, ocular irritation, and ocular discharge) to a greater degree than the alternative tear supplement (P = 0.0003). Further, owners reported the xCMHA-S treatment as being more highly effective than the alternative tear supplement (P = 0.0024). These results further demonstrate the efficacy of the xCMHA-S in reducing the clinical signs associated with KCS, thereby improving patient health and owner happiness.

Bringing a Perspective from Outside the Field: A Commentary on Davis et al.'s (2010) Use of a Modified Regression Discontinuity Design to Evaluate a Gifted Program

ERIC Educational Resources Information Center

Adelson, Jill L.; Kelcey, Benjamin

2016-01-01

In this commentary of "Evaluating the Gifted Program of an Urban School District Using a Modified Regression Discontinuity Design" by Davis, Engberg, Epple, Sieg, and Zimmer, we examine the background of the study, critique the methods used, and discuss the results and implications. The study used a fuzzy regression discontinuity design…

Reliability of the Phi angle to assess rotational alignment of the talar component in total ankle replacement.

PubMed

Manzi, Luigi; Villafañe, Jorge Hugo; Indino, Cristian; Tamini, Jacopo; Berjano, Pedro; Usuelli, Federico Giuseppe

2017-11-08

The purpose of this study was to investigate the test-retest reliability of the Phi angle in patients undergoing total ankle replacement (TAR) for end stage ankle osteoarthritis (OA) to assess the rotational alignment of the talar component. Retrospective observational cross-sectional study of prospectively collected data. Post-operative anteroposterior radiographs of the foot of 170 patients who underwent TAR for the ankle OA were evaluated. Three physicians measured Phi on the 170 randomly sorted and anonymized radiographs on two occasions, one week apart (test and retest conditions), inter and intra-observer agreement were evaluated. Test-retest reliability of Phi angle measurement was excellent for patients with Hintegra TAR (ICC=0.995; p<0.001) and Zimmer TAR (ICC=0.995; p<0.001) on radiographs of subjects with ankle OA. There were no significant differences in the reliability of the Phi angle measurement between patients with Hintegra vs. Zimmer implants (p>0.05). Measurement of Phi angle on weight-bearing dorsoplantar radiograph showed an excellent reliability among orthopaedic surgeons in determining the position of the talar component in the axial plane. Level II, cross sectional study. Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Outcomes for a large metaphyseal volume hemiarthroplasty in complex fractures of the proximal humerus.

PubMed

White, Jonathan J E; Soothill, John R; Morgan, Marie; Clark, David I; Espag, Marius P; Tambe, Amol A

2017-03-01

A large metaphyseal volume shoulder hemiarthroplasty has been in use within our department since 2008; however, no clinical outcome data are available for this prosthesis apart from the designer surgeon series. During a 5-year period, data were collected for 40 patients (30 women, 10 men) treated consecutively with the Zimmer Anatomical Shoulder Fracture hemiarthroplasty system (Zimmer, Warsaw, IN, USA). The final analysis included 26 patients. The median age was 79 years (range, 58-91 years), and the median follow-up was 3.7 years (range, 2.0-5.8 years). The median Constant Score was 34 points (range, 16-70 points), and the median Oxford Shoulder Score was 27 points (range, 5-46 points). The greater tuberosity healed satisfactorily in 12 patients. Resorption of the greater tuberosity was seen radiologically in 18 patients. The presence of resorption had no significant effect on the Constant Score (P = .264) or the Oxford Shoulder Score (P = .469). Three patients (12%) required revision. This is the first report from a nondesigner center for outcomes for this prosthesis to date. The results demonstrate reduced functional performance compared with the designer series. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Mechanical characterization and modeling of sponge-reinforced hydrogel composites under compression.

PubMed

Wu, Lei; Mao, Guoyong; Nian, Guodong; Xiang, Yuhai; Qian, Jin; Qu, Shaoxing

2018-05-30

Load-bearing applications of hydrogels call for materials with excellent mechanical properties. Despite the considerable progress in developing tough hydrogels, there is still a requirement to prepare high-performance hydrogels using simple strategies. In this paper, a sponge-reinforced hydrogel composite is synthesized by combining poly(acrylamide) (PAAm) hydrogel and polyurethane (PU) sponge. Uniaxial compressive testing of the hydrogel composites reveals that both the compressive modulus and the strength of the hydrogel composites are much higher than those of the PAAm hydrogel or sponge. In order to predict the compressive modulus of the hydrogel composite, we develop a theoretical model that is validated by experiments and numerical simulations. The present work may guide the design and manufacture of hydrogel-based composite materials, especially for biomaterial scaffolds and soft transducers.

Nitric Oxide Stimulates Matrix Synthesis and Deposition by Adult Human Aortic Smooth Muscle Cells Within Three-Dimensional Cocultures

PubMed Central

Simmers, Phillip; Gishto, Arsela; Vyavahare, Narendra

2015-01-01

Vascular diseases are characterized by the over-proliferation and migration of aortic smooth muscle cells (SMCs), and degradation of extracellular matrix (ECM) within the vessel wall, leading to compromise in cell–cell and cell–matrix signaling pathways. Tissue engineering approaches to regulate SMC over-proliferation and enhance healthy ECM synthesis showed promise, but resulted in low crosslinking efficiency. Here, we report the benefits of exogenous nitric oxide (NO) cues, delivered from S-Nitrosoglutathione (GSNO), to cell proliferation and matrix deposition by adult human aortic SMCs (HA-SMCs) within three-dimensional (3D) biomimetic cocultures. A coculture platform with two adjacent, permeable 3D culture chambers was developed to enable paracrine signaling between vascular cells. HA-SMCs were cultured in these chambers within collagen hydrogels, either alone or in the presence of human aortic endothelial cells (HA-ECs) cocultures, and exogenously supplemented with varying GSNO dosages (0–100 nM) for 21 days. Results showed that EC cocultures stimulated SMC proliferation within GSNO-free cultures. With increasing GSNO concentration, HA-SMC proliferation decreased in the presence or absence of EC cocultures, while HA-EC proliferation increased. GSNO (100 nM) significantly enhanced the protein amounts synthesized by HA-SMCs, in the presence or absence of EC cocultures, while lower dosages (1–10 nM) offered marginal benefits. Multi-fold increases in the synthesis and deposition of elastin, glycosaminoglycans, hyaluronic acid, and lysyl oxidase crosslinking enzyme (LOX) were noted at higher GSNO dosages, and coculturing with ECs significantly furthered these trends. Similar increases in TIMP-1 and MMP-9 levels were noted within cocultures with increasing GSNO dosages. Such increases in matrix synthesis correlated with NO-stimulated increases in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression within EC and SMC cultures, respectively. Results attest to the benefits of delivering NO cues to suppress SMC proliferation and promote robust ECM synthesis and deposition by adult human SMCs, with significant applications in tissue engineering, biomaterial scaffold development, and drug delivery. PMID:25597545

Peptide hydrogelation triggered by enzymatic induced pH switch

NASA Astrophysics Data System (ADS)

Cheng, Wei; Li, Ying

2016-07-01

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

Transparent hydrogel with enhanced water retention capacity by introducing highly hydratable salt

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

Bai, Yuanyuan; Xiang, Feng; Wang, Hong, E-mail: hwang@mail.xjtu.edu.cn, E-mail: suo@seas.harvard.edu

2014-10-13

Polyacrylamide hydrogels containing salt as electrolyte have been used as highly stretchable transparent electrodes in flexible electronics, but those hydrogels are easy to dry out due to water evaporation. Targeted, we try to enhance water retention capacity of polyacrylamide hydrogel by introducing highly hydratable salts into the hydrogel. These hydrogels show enhanced water retention capacity in different level. Specially, polyacrylamide hydrogel containing high content of lithium chloride can retain over 70% of its initial water even in environment with relative humidity of only 10% RH. The excellent water retention capacities of these hydrogels will make more applications of hydrogels becomemore » possible.« less

Introduction to cell–hydrogel mechanosensing

PubMed Central

Ahearne, Mark

2014-01-01

The development of hydrogel-based biomaterials represents a promising approach to generating new strategies for tissue engineering and regenerative medicine. In order to develop more sophisticated cell-seeded hydrogel constructs, it is important to understand how cells mechanically interact with hydrogels. In this paper, we review the mechanisms by which cells remodel hydrogels, the influence that the hydrogel mechanical and structural properties have on cell behaviour and the role of mechanical stimulation in cell-seeded hydrogels. Cell-mediated remodelling of hydrogels is directed by several cellular processes, including adhesion, migration, contraction, degradation and extracellular matrix deposition. Variations in hydrogel stiffness, density, composition, orientation and viscoelastic characteristics all affect cell activity and phenotype. The application of mechanical force on cells encapsulated in hydrogels can also instigate changes in cell behaviour. By improving our understanding of cell–material mechano-interactions in hydrogels, this should enable a new generation of regenerative medical therapies to be developed. PMID:24748951

Unconventional Tough Double-Network Hydrogels with Rapid Mechanical Recovery, Self-Healing, and Self-Gluing Properties.

PubMed

Jia, Haiyan; Huang, Zhangjun; Fei, Zhaofu; Dyson, Paul J; Zheng, Zhen; Wang, Xinling

2016-11-16

Hydrogels are polymeric materials that have a relatively high capacity for holding water. Recently, a double network (DN) technique was developed to fabricate hydrogels with a toughness comparable to rubber. The mechanical properties of DN hydrogels may be attributed to the brittle sacrificial bonding network of one hydrogel, facilitating stress dispersion, combined with ductile polymer chains of a second hydrogel. Herein, we report a novel class of tunable DN hydrogels composed of a polyurethane hydrogel and a stronger, dipole-dipole and H-bonding interaction reinforced (DHIR) hydrogel. Compared to conventional DN hydrogels, these materials show remarkable improvements in mechanical recovery, modulus, and yielding, with excellent self-healing and self-gluing properties. In addition, the new DN hydrogels exhibit excellent tensile and compression strengths and possess shape-memory properties, which make them promising for applications in engineering, biomedicine, and other domains where load bearing is required.

Heart Rate Variability and Cardiovascular Reactivity in Panic Disorder

DTIC Science & Technology

1999-04-01

pharmacological treatment with alprazolam or clonidine (Klein, Cnaani et al., 1995), or paroxetine (Tucker et al., 1997) were found not to differ...of Cardiology, 60, 86-89. Mcleod, D. R., Hoehn-Saric, R., Zimmerli, W.D. De Souza, E. B. & Oliver, L. K. (1990). Treatment effects of alprazolam and...and alprazolam effects on stress test reactivity in panic disorder. Biological Psychiatry. 31, 35-51. Roth, W. T., Margraf, J., Ehlers, A., Taylor

Gifted Identification and the Role of Gifted Education: A Commentary on "Evaluating the Gifted Program of an Urban School District Using a Modified Regression Discontinuity Design"

ERIC Educational Resources Information Center

Steenbergen-Hu, Saiying; Olszewski-Kubilius, Paula

2016-01-01

The article by Davis, Engberg, Epple, Sieg, and Zimmer (2010) represents one of the recent research efforts from economists in evaluating the impact of gifted programs. It can serve as a worked example of the implementation of the regression discontinuity (RD) design method in gifted education research. In this commentary, we first illustrate the…

Complement Receptor 1 Is a Sialic Acid-Independent Erythrocyte Receptor of Plasmodium falciparum

DTIC Science & Technology

2010-06-17

Pennsylvania State University College of Medicine, Hershey , Pennsylvania, United States of America Abstract Plasmodium falciparum is a highly lethal malaria...www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000968 Zimmerli S, Edwards S, Ernst JD ( 1996 ) Selective receptor blockade...in field isolates. J Immunol 165: 6341–6346. 22. Baruch DI, Gormely JA, Ma C, Howard RJ, Pasloske BL ( 1996 ) Plasmodium falciparum erythrocyte

Preparation of keratin and chemically modified keratin hydrogels and their evaluation as cell substrate with drug releasing ability.

PubMed

Nakata, Ryo; Osumi, Yu; Miyagawa, Shoko; Tachibana, Akira; Tanabe, Toshizumi

2015-07-01

Keratin was extracted as a reduced form from wool, which was then subjected to acetamidation, carboxymethylation or aminoethylation at abundant free cysteine residues to give acetamidated keratin (AAK), carboxymethylated keratin (CMK) and aminoethylated keratin (AEK). Hydrogels were prepared from intact and three chemically modified keratins simply by concentrating their aqueous solution and subsequent cooling. The lowest concentration to form a hydrogel without fluidity was 110 mg/ml for AAK, 120 mg/ml for AEK, 130 mg/ml for keratin and 180 mg/ml for CMK. Comparing with a hydrogel just prepared (swelling ratio: 600-700), each hydrogel slightly shrank in an acidic solution. While AAK hydrogel little swelled in neutral and basic solutions, other hydrogels became swollen and CMK hydrogel reached to dissolution. Hydrogels of keratin, AAK and AEK were found to support cell proliferation, although cell elongation on AAK and AEK hydrogel was a little suppressed. On the other hand, CMK hydrogel did not seem to be suitable for a cell substrate because of its high swelling in culture medium. Evaluation of the hydrogels as a drug carrier showed that keratin and AAK hydrogels were good sustained drug release carriers, which showed the drug release for more than three days, while the release from AEK and CMK hydrogels completed within one day. Thus, keratin and chemically modified keratin hydrogels, especially keratin and AAK hydrogels, were promising biomaterials as a cell substrate and a sustained drug release carrier. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Hydrogels for Hydrophobic Drug Delivery. Classification, Synthesis and Applications

PubMed Central

Stewart, Sarah; Ervine, Michael; Al-Kasasbeh, Rehan; Donnelly, Ryan F.

2018-01-01

Hydrogels have been shown to be very useful in the field of drug delivery due to their high biocompatibility and ability to sustain delivery. Therefore, the tuning of their properties should be the focus of study to optimise their potential. Hydrogels have been generally limited to the delivery of hydrophilic drugs. However, as many of the new drugs coming to market are hydrophobic in nature, new approaches for integrating hydrophobic drugs into hydrogels should be developed. This article discusses the possible new ways to incorporate hydrophobic drugs within hydrogel structures that have been developed through research. This review describes hydrogel-based systems for hydrophobic compound delivery included in the literature. The section covers all the main types of hydrogels, including physical hydrogels and chemical hydrogels. Additionally, reported applications of these hydrogels are described in the subsequent sections. PMID:29364833

Adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis to silicone-hydrogel contact lenses.

PubMed

Henriques, Mariana; Sousa, Cláudia; Lira, Madalena; Elisabete, M; Oliveira, Real; Oliveira, Rosário; Azeredo, Joana

2005-06-01

The purpose of this study is to compare the adhesion capabilities of the most important etiologic agents of microbial ocular infection to the recently available silicone-hydrogel lenses with those to a conventional hydrogel lens. In vitro static adhesion assays of Pseudomonas aeruginosa 10,145, Staphylococcus epidermidis 9142 (biofilm-positive), and 12,228 (biofilm-negative) to two extended-wear silicone-hydrogel lenses (balafilcon A and lotrafilcon A), a daily wear silicone-hydrogel lens (galyfilcon A) and a conventional hydrogel (etafilcon A) were performed. To interpret the adhesion results, lens surface relative hydrophobicity was assessed by water contact angle measurements. P. aeruginosa and S. epidermidis 9142 exhibited greater adhesion capabilities to the extended wear silicone-hydrogel lenses than to the daily wear silicone- and conventional hydrogel lenses (p < 0.05). No statistical differences were found between the adhesion extent of these strains to galyfilcon A and etafilcon A. The biofilm negative strain of S. epidermidis adhered in larger extents to the silicone-hydrogel lenses than to the conventional hydrogel (p < 0.05), but in much lower amounts than the biofilm-positive strain. The water contact angle measurements revealed that the extended wear silicone-hydrogel lenses are hydrophobic, whereas the daily wear silicone- and conventional hydrogel lenses are hydrophilic. As a result of their hydrophobicity, the extended wear silicone-hydrogel lenses (lotrafilcon A and balafilcon A) may carry higher risk of microbial contamination than both the hydrophilic daily wear silicone-hydrogel lens, galyfilcon A and the conventional hydrogel lens, etafilcon A.

Sundew-Inspired Adhesive Hydrogels Combined with Adipose-Derived Stem Cells for Wound Healing

PubMed Central

Sun, Leming; Huang, Yujian; Bian, Zehua; Petrosino, Jennifer; Fan, Zhen; Wang, Yongzhong; Park, Ki Ho; Yue, Tao; Schmidt, Michael; Galster, Scott; Ma, Jianjie; Zhu, Hua; Zhang, Mingjun

2016-01-01

The potential to harness the unique physical, chemical, and biological properties of the sundew (Drosera) plant’s adhesive hydrogels has long intrigued researchers searching for novel wound-healing applications. However, the ability to collect sufficient quantities of the sundew plant’s adhesive hydrogels is problematic and has eclipsed their therapeutic promise. Inspired by these natural hydrogels, we asked if sundew-inspired adhesive hydrogels could overcome the drawbacks associated with natural sundew hydrogels and be used in combination with stem-cell-based therapy to enhance wound-healing therapeutics. Using a bioinspired approach, we synthesized adhesive hydrogels comprised of sodium alginate, gum arabic, and calcium ions to mimic the properties of the natural sundew-derived adhesive hydrogels. We then characterized and showed that these sundew-inspired hydrogels promote wound healing through their superior adhesive strength, nanostructure, and resistance to shearing when compared to other hydrogels in vitro. In vivo, sundew-inspired hydrogels promoted a “suturing” effect to wound sites, which was demonstrated by enhanced wound closure following topical application of the hydrogels. In combination with mouse adipose-derived stem cells (ADSCs) and compared to other therapeutic biomaterials, the sundew-inspired hydrogels demonstrated superior wound-healing capabilities. Collectively, our studies show that sundew-inspired hydrogels contain ideal properties that promote wound healing and suggest that sundew-inspired-ADSCs combination therapy is an efficacious approach for treating wounds without eliciting noticeable toxicity or inflammation. PMID:26731614

Sundew-Inspired Adhesive Hydrogels Combined with Adipose-Derived Stem Cells for Wound Healing.

PubMed

Sun, Leming; Huang, Yujian; Bian, Zehua; Petrosino, Jennifer; Fan, Zhen; Wang, Yongzhong; Park, Ki Ho; Yue, Tao; Schmidt, Michael; Galster, Scott; Ma, Jianjie; Zhu, Hua; Zhang, Mingjun

2016-01-27

The potential to harness the unique physical, chemical, and biological properties of the sundew (Drosera) plant's adhesive hydrogels has long intrigued researchers searching for novel wound-healing applications. However, the ability to collect sufficient quantities of the sundew plant's adhesive hydrogels is problematic and has eclipsed their therapeutic promise. Inspired by these natural hydrogels, we asked if sundew-inspired adhesive hydrogels could overcome the drawbacks associated with natural sundew hydrogels and be used in combination with stem-cell-based therapy to enhance wound-healing therapeutics. Using a bioinspired approach, we synthesized adhesive hydrogels comprised of sodium alginate, gum arabic, and calcium ions to mimic the properties of the natural sundew-derived adhesive hydrogels. We then characterized and showed that these sundew-inspired hydrogels promote wound healing through their superior adhesive strength, nanostructure, and resistance to shearing when compared to other hydrogels in vitro. In vivo, sundew-inspired hydrogels promoted a "suturing" effect to wound sites, which was demonstrated by enhanced wound closure following topical application of the hydrogels. In combination with mouse adipose-derived stem cells (ADSCs) and compared to other therapeutic biomaterials, the sundew-inspired hydrogels demonstrated superior wound-healing capabilities. Collectively, our studies show that sundew-inspired hydrogels contain ideal properties that promote wound healing and suggest that sundew-inspired-ADSCs combination therapy is an efficacious approach for treating wounds without eliciting noticeable toxicity or inflammation.

Electrochemical immunoassay for tumor markers based on hydrogels.

PubMed

Yin, Shuang; Ma, Zhanfang

2018-05-08

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

On the Interaction between Superabsorbent Hydrogels and Cementitious Materials

NASA Astrophysics Data System (ADS)

Farzanian, Khashayar

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

Mechanical Behavior of Tough Hydrogels for Structural Applications

NASA Astrophysics Data System (ADS)

Illeperuma, Widusha Ruwangi Kaushalya

Hydrogels are widely used in many commercial products including Jell-O, contact lenses, and superabsorbent diapers. In recent decades, hydrogels have been under intense development for biomedical applications, such as scaffolds in tissue engineering, carriers for drug delivery, and valves in microfluidic systems. But the scope is severely limited as conventional hydrogels are weak and brittle and are not very stretchable. This thesis investigates the approaches that enhance the mechanical properties of hydrogels and their structural applications. We discov¬ered a class of exceptionally stretchable and tough hydrogels made from poly-mers that form networks via ionic and covalent crosslinks. Although such a hydrogel contains ~90% water, it can be stretched beyond 20 times its initial length, and has a fracture energy of ~9000 J/m2. The combination of large stretchability, remarkable toughness, and recoverability of stiffness and toughness, along with easy synthesis makes this material much superior over existing hydrogels. Extreme stretchability and blunted crack tips of these hydrogels question the validity of traditional fracture testing methods. We re-examine a widely used pure shear test method to measure the fracture energy. With the experimental and simulation results, we conclude that the pure shear test method can be used to measure fracture energy of extremely stretchable materials. Even though polyacrylamide-alginate hydrogels have an extremely high toughness, it has a relatively low stiffness and strength. We improved the stiffness and strength by embedding fibers. Most hydrogels are brittle, allowing the fibers to cut through the hydrogel when the composite is loaded. But tough hydrogel composites do not fail by the fibers cutting the hydrogel; instead, it undergoes large deforming by fibers sliding through the matrix. Hydrogels were not considered as materials for structural applications. But with enhanced mechanical properties, they have opened up 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.

Biomimetic hydrogel loaded with silk and l-proline for tissue engineering and wound healing applications.

PubMed

Thangavel, Ponrasu; Ramachandran, Balaji; Kannan, Ramya; Muthuvijayan, Vignesh

2017-08-01

The aim of this article was to develop silk protein (SF) and l-proline (LP) loaded chitosan-(CS) based hydrogels via physical cross linking for tissue engineering and wound healing applications. Silk fibroin, a biodegradable and biocompatible protein, and l-proline, an important imino acid that is required for collagen synthesis, were added to chitosan to improve the wound healing properties of the hydrogel. Characterization of these hydrogels revealed that CS/SF/LP hydrogels were blended properly and LP incorporated hydrogels showed excellent thermal stability and good surface morphology. Swelling study showed the water holding efficiency of the hydrogels to provide enough moisture at the wound surface. In vitro biodegradation results demonstrated that the hydrogels had good degradation rate in PBS with lysozyme. LP loaded hydrogels showed approximately a twofold increase in antioxidant activity. In vitro cytocompatibility studies using NIH 3T3 L1 cells showed increased cell viability (p < 0.01), migration, proliferation and wound healing activity (p < 0.001) in LP loaded hydrogels compared to CS and CS/SF hydrogels. Cell adhesion on SF and LP hydrogels were observed using SEM and compared to CS hydrogel. LP incorporation showed 74-78% of wound closure compared to 35% for CS/SF and 3% for CS hydrogels at 48 h. These results suggest that incorporation of LP can significantly accelerate wound healing process compared to pure CS and SF-loaded CS hydrogels. Hence, CS/LP hydrogels could be a potential wound dressing material for the enhanced wound tissue regeneration and repair. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1401-1408, 2017. © 2016 Wiley Periodicals, Inc.

Friction of sodium alginate hydrogel scaffold fabricated by 3-D printing.

PubMed

Yang, Qian; Li, Jian; Xu, Heng; Long, Shijun; Li, Xuefeng

2017-04-01

A rapid prototyping technology, formed by three-dimensional (3-D) printing and then crosslinked by spraying Ca 2+ solution, is developed to fabricate a sodium alginate (SA) hydrogel scaffold. The porosity, swelling ratio, and compression modulus of the scaffold are investigated. A friction mechanism is developed by studying the reproducible friction behavior. Our results show that the scaffold can have 3-D structure with a porosity of 52%. The degree of swelling of the SA hydrogel scaffold is 8.5, which is nearly the same as bulk SA hydrogel. SA hydrogel exhibits better compressive resilience than bulk hydrogel despite its lower compressive modulus compared to bulk hydrogel. The SA hydrogel scaffold exhibits a higher frictional force at low sliding velocity (10 -6 to 10 -3  m/s) compared to bulk SA hydrogel, and they are equal at high sliding velocity (10 -2 to 1 m/s). For a small pressure (0.3 kPa), the SA hydrogel scaffold shows good friction reproducibility. In contrast, bulk SA hydrogel shows poor reproducibility with respect to friction behavior. The differences in friction behaviors between the SA hydrogel scaffold and bulk SA hydrogel are related to the structure of the scaffold, which can keep a stable hydrated lubrication layer.

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.

Cross-Linked Hydrogel for Pharmaceutical Applications: A Review

PubMed Central

2017-01-01

Hydrogels are promising biomaterials because of their important qualities such as biocompatibility, biodegradability, hydrophilicity and non-toxicity. These qualities make hydrogels suitable for application in medical and pharmaceutical field. Recently, a tremendous growth of hydrogel application is seen, especially as gel and patch form, in transdermal drug delivery. This review mainly focuses on the types of hydrogels based on cross-linking and; secondly to describe the possible synthesis methods to design hydrogels for different pharmaceutical applications. The synthesis and chemistry of these hydrogels are discussed using specific pharmaceutical examples. The structure and water content in a typical hydrogel have also been discussed. PMID:29399542

Supramolecular Hydrogelators and Hydrogels: From Soft Matter to Molecular Biomaterials

PubMed Central

2015-01-01

In this review we intend to provide a relatively comprehensive summary of the work of supramolecular hydrogelators after 2004 and to put emphasis particularly on the applications of supramolecular hydrogels/hydrogelators as molecular biomaterials. After a brief introduction of methods for generating supramolecular hydrogels, we discuss supramolecular hydrogelators on the basis of their categories, such as small organic molecules, coordination complexes, peptides, nucleobases, and saccharides. Following molecular design, we focus on various potential applications of supramolecular hydrogels as molecular biomaterials, classified by their applications in cell cultures, tissue engineering, cell behavior, imaging, and unique applications of hydrogelators. Particularly, we discuss the applications of supramolecular hydrogelators after they form supramolecular assemblies but prior to reaching the critical gelation concentration because this subject is less explored but may hold equally great promise for helping address fundamental questions about the mechanisms or the consequences of the self-assembly of molecules, including low molecular weight ones. Finally, we provide a perspective on supramolecular hydrogelators. We hope that this review will serve as an updated introduction and reference for researchers who are interested in exploring supramolecular hydrogelators as molecular biomaterials for addressing the societal needs at various frontiers. PMID:26646318

Chitin-natural clay nanotubes hybrid hydrogel.

PubMed

Liu, Mingxian; Zhang, Yun; Li, Jingjing; Zhou, Changren

2013-07-01

Novel hybrid hydrogel was synthesized from chitin NaOH/urea aqueous solution in presence of halloysite nanotubes (HNTs) via crosslinking with epichlorohydrin. Fourier transform infrared (FT-IR) spectra and atomic force microscopy (AFM) results confirmed the interfacial interactions in the chitin-HNTs hybrid hydrogel. The compressive strength and shear modulus of chitin hydrogel were significantly increased by HNTs as shown in the static compressive experiment and rheology measurement. The hybrid hydrogels showed highly porous microstructures by scanning electron microscopy (SEM). The swelling ratio of chitin hydrogel decreased because of the addition of HNTs. The malachite green's absorption experiment result showed that the hybrid hydrogel exhibited much higher absorption rate than the pure chitin hydrogel. The prepared hybrid hydrogel had potential applications in waste treatment and biomedical areas. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Metallated DNA Aptamers for Prostate Cancer Treatment

DTIC Science & Technology

2013-03-01

minor groove while the new 320 nm maxima reflect the binding of N-methyl pyrrole moieties of netropsin in the minor groove of 3’FdU.(Zimmer, Marck...resonance assignment and those consistent with the pyrrole 1 H resonances of netropsin (Fig. 3). NOESY crosspeaks from FdU imino 1 H to putative...computational chemistry data from our laboratory and with netropsin binding in the minor groove based upon NOE data from pyrrole 1 H of netropsin and

Effect of Broadband Nature of Marine Mammal Echolocation Clicks on Click-Based Population Density Estimates

DTIC Science & Technology

2015-09-30

sonar sound and therefore of high relevance to the US Navy, and sperm whale (Physeter macrocephalus) clicks, whose high source level assures long...beaked whale, and Zimmer (2011) for the sperm whale. 5 For background noise we used measurements obtained with the Delphinus towed array at the US...Atlantic Undersea Test and Evaluation Center (AUTEC), where both Blainville’s beaked whales and sperm whales are commonly present. Analysis of the

Archaeological Investigations at the Grant River Public Use Area. Volume 1. Narrative.

DTIC Science & Technology

1984-12-01

St. Paul, Minnesota 55101-1479 Ms. Patricia Emerson Impact Services, Inc. P.O. Box 3224 Mankato, Minnesota 56001 Mr. Alan Van Dyke Berg- Zimmer and...biface was recovered. It is basally thinned with very weak shoulders . No grinding occurs on either the lateral margins or on the concave base... anatomical elements (see Appendix C). A minimum number of individuals is 16, based on the most frequently occurring element, the right mandibular first molar

Synthesis and characterization of arginine-NIPAAm hybrid hydrogel as wound dressing: In vitro and in vivo study.

PubMed

Wu, De-Qun; Zhu, Jie; Han, Hua; Zhang, Jun-Zhi; Wu, Fei-Fei; Qin, Xiao-Hong; Yu, Jian-Yong

2018-01-01

A multi-functional hybrid hydrogel P(M-Arg/NIPAAm) with temperature response, anti-protein adsorption and antibacterial properties was prepared and applied as wound dressing. The hydrogel was carried out by free radical copolymerization of methacrylate arginine (M-Arg) and N-isopropyl acrylamide (NIPAAm) monomers using N,N'-methylene bisacrylamide as a crosslinker, and ammonium persulfate/N,N,N', N'-tetramethylethylenediamine as the redox initiator. To endow the antimicrobial property, chlorhexidine diacetate (CHX) was preloaded into the hydrogel and polyhexamethylene guanidine phosphate (PHMG) was grafted on the hydrogel surface, respectively. The antimicrobial property of two series of hydrogels was evaluated and compared. The successful synthesis of M-Arg, PHMG and hydrogels was proved by 13 C NMR, 1 H NMR and FTIR spectroscopy. The hydrogel morphology characterized by scanning electron microscopy confirmed that the homogeneous porous and interconnected structures of the hydrogels. The swelling, protein adsorption property, in vitro release of CHX, antimicrobial assessment, cell viability as well as in vivo wound healing in a mouse model were studied. The results showed the nontoxicity and antimicrobial P(M-Arg/NIPAAm) hydrogel accelerated the full-thickness wound healing process and had the potential application in wound dressing. Despite the zwitterionic characteristic and biocompatible property of arginine based hydrogels, the brittle behavior and non-transparency still remain as a significant problem for wound dressing. Furthermore promoting the antibacterial property of the zwitterionic hydrogel is also necessary to prevent the bacterial colonization and subsequent wound infection. Therefore, we created a hybrid hydrogel combined methacrylate arginine (M-Arg) and N-isopropyl acrylamide (NIPAAm). NIPAAm improves transparency and mechanical property as well as acts as a temperature-response drug release system. Additionally, chlorhexidine (CHX) was preloaded into the hydrogels and polyhexamethylene guanidine phosphate (PHMG) was grafted on the hydrogel surface, respectively, which make the hydrogel useful as a favorable antibacterial dressing. The hybrid hydrogel has a combination effect of biocompatibility, environmentally responsive transformation behavior, biodegradability, anti-protein adsorption and antimicrobial properties. This report proposes the preparation of P(M-Arg/NIPAAm) hydrogel that has a great potential for wound healing. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Mechanically enhanced nested-network hydrogels as a coating material for biomedical devices.

PubMed

Wang, Zhengmu; Zhang, Hongbin; Chu, Axel J; Jackson, John; Lin, Karen; Lim, Chinten James; Lange, Dirk; Chiao, Mu

2018-04-01

Well-organized composite formations such as hierarchical nested-network (NN) structure in bone tissue and reticular connective tissue present remarkable mechanical strength and play a crucial role in achieving physical and biological functions for living organisms. Inspired by these delicate microstructures in nature, an analogous scaffold of double network hydrogel was fabricated by creating a poly(2-hydroxyethyl methacrylate) (pHEMA) network in the porous structure of alginate hydrogels. The resulting hydrogel possessed hierarchical NN structure and showed significantly improved mechanical strength but still maintained high elasticity comparable to soft tissues due to a mutual strengthening effect between the two networks. The tough hydrogel is also self-lubricated, exhibiting a surface friction coefficient comparable with polydimethylsiloxane (PDMS) substrates lubricated by a commercial aqueous lubricant (K-Y Jelly) and other low surface friction hydrogels. Additional properties of this hydrogel include high hydrophilicity, good biocompatibility, tunable cell adhesion and bacterial resistance after incorporation of silver nanoparticles. Firm bonding of the hydrogel on silicone substrates could be achieved through facile chemical modification, thus enabling the use of this hydrogel as a versatile coating material for biomedical applications. In this study, we developed a tough hydrogel by crosslinking HEMA monomers in alginate hydrogels and forming a well-organized structure of hierarchical nested network (NN). Different from most reported stretchable alginate-based hydrogels, the NN hydrogel shows higher compressive strength but retains comparable softness to alginate counterparts. This work further demonstrated the good integration of the tough hydrogel with silicone substrates through chemical modification and micropillar structures. Other properties including surface friction, biocompatibility and bacterial resistance were investigated and the hydrogel shows a great promise as a versatile coating material for biomedical applications. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2012-06-20

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

Hydrogel-Based Drug Delivery Systems for Poorly Water-Soluble Drugs.

PubMed

McKenzie, Matthew; Betts, David; Suh, Amy; Bui, Kathryn; Kim, London Doyoung; Cho, Hyunah

2015-11-13

Hydrogels are three-dimensional materials that can withstand a great amount of water incorporation while maintaining integrity. This allows hydrogels to be very unique biomedical materials, especially for drug delivery. Much effort has been made to incorporate hydrophilic molecules in hydrogels in the field of drug delivery, while loading of hydrophobic drugs has not been vastly studied. However, in recent years, research has also been conducted on incorporating hydrophobic molecules within hydrogel matrices for achieving a steady release of drugs to treat various ailments. Here, we summarize the types of hydrogels used as drug delivery vehicles, various methods to incorporate hydrophobic molecules in hydrogel matrices, and the potential therapeutic applications of hydrogels in cancer.

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

PubMed

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

2016-09-01

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

Facile synthesis of degradable and electrically conductive polysaccharide hydrogels.

PubMed

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

2011-07-11

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

Green synthesis of tea Ag nanocomposite hydrogels via mint leaf extraction for effective antibacterial activity.

PubMed

Jayaramudu, Tippabattini; Varaprasad, Kokkarachedu; Raghavendra, Gownolla Malegowd; Sadiku, E R; Mohana Raju, Konduru; Amalraj, John

2017-10-01

In this report, we investigated the swelling behavior and antibacterial property of nanosilver composite hydrogels made from tea with polyacrylamide via a free-radical polymerization and green process technique. This is probably for the first time; tea-based nano silver composite hydrogels were developed. The composite hydrogels comprise embedded nano silver particles in the tea hydrogel matrix via a green process with mint leaf extract. The size of the nano silver particles in the hydrogel matrix was found to be < 10 nm. The nano silver composite hydrogels formed and their blank hydrogels from the mint leaf were characterized by using ultraviolet-visible spectroscopy, scanning electron microscopy with energy dispersive spectroscopy, transmission electron microscopy, thermogravimetric analysis and X-ray diffraction studies. The nano silver composite hydrogels developed exhibit eminent antibacterial activity against Escherichia coli and Staphylococcus aureus. This clearly indicates that the nano silver composite hydrogels are potential candidates for antimicrobial applications.

Tough bonding of hydrogels to diverse non-porous surfaces

NASA Astrophysics Data System (ADS)

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

2016-02-01

In many animals, the bonding of tendon and cartilage to bone is extremely tough (for example, interfacial toughness ~800 J m-2 refs ,), yet such tough interfaces have not been achieved between synthetic hydrogels and non-porous surfaces of engineered solids. Here, we report a strategy to design tough transparent and conductive bonding of synthetic hydrogels containing 90% water to non-porous surfaces of diverse solids, including glass, silicon, ceramics, titanium and aluminium. The design strategy is to anchor the long-chain polymer networks of tough hydrogels covalently to non-porous solid surfaces, which can be achieved by the silanation of such surfaces. Compared with physical interactions, the chemical anchorage results in a higher intrinsic work of adhesion and in significant energy dissipation of bulk hydrogel during detachment, which lead to interfacial toughness values over 1,000 J m-2. We also demonstrate applications of robust hydrogel-solid hybrids, including hydrogel superglues, mechanically protective hydrogel coatings, hydrogel joints for robotic structures and robust hydrogel-metal conductors.

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

PubMed

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

2018-07-01

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

Synthesis and characterization of hydrogel films of carboxymethyl tamarind gum using citric acid.

PubMed

Mali, Kailas K; Dhawale, Shashikant C; Dias, Remeth J

2017-12-01

The objective of this study was to synthesize and characterize citric acid crosslinked carboxymethyl tamarind gum (CMTG) hydrogels films. The hydrogel films were characterized by Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, solid state 13 C-nuclear magnetic resonance ( 13 C NMR) spectroscopy and differential scanning calorimeter (DSC). The prepared hydrogel films were evaluated for the carboxyl content and swelling ratio. The model drug moxifloxacin hydrochloride was loaded into hydrogels films and drug release was studied at pH 7.4. The hemolysis assay was used to study the biocompatibility of hydrogel films. The results of ATR-FTIR, solid state 13 C NMR and DSC confirmed the formation of ester crosslinks between citric acid and CMTG. The total carboxyl content of hydrogel film was found to be decreased when amount of CMTG was increased. The swelling of hydrogel film was found to be decreased with increase in curing temperature and time. CMTG hydrogel films showed high drug loading with non-Fickian release mechanism suggesting controlled release of drug. The hydrogel films were found to be biocompatible. It can be concluded that the citric acid can be used for the preparation of CMTG hydrogel films. Further, CMTG hydrogel film can be used potentially for controlled release of drug. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2017-01-01

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

Efforts to eradicate yellow crazy ants on Johnston Atoll: Results from crazy ant strike teams X, XI and XII (June 2015–December 2016)

USGS Publications Warehouse

Peck, Robert W; Banko, Paul C.; Donmoyer, Kevin; Scheiner, Katrina; Karimi, Rebekah; Kropidlowski, Stefan

2017-01-01

Efforts to eradicate invasive yellow crazy ants (Anoplolepis gracilipes; YCA) on Johnston Atoll have been continuous since their discovery in 2010. Through 2014, a variety of commercial and novel formicidal baits were tested against the ant, but none proved capable of eradication. More recently, polyacrylamide crystals (“hydrogel”) saturated with a sucrose solution containing the insecticide dinotefuran has been shown to be effective over large areas when applied against YCA alone or sequentially with a protein-based cat food bait. During June 2015–December 2016, Crazy Ant Strike Teams (CASTs) conducted treatment and monitoring efforts across an infestation of about 57 ha on Johnston Atoll. Following three infestation-wide treatments (primarily using hydrogel) during 2015, YCA were reduced 98% and surviving nests became difficult to find. Subsequently, a protocol designed to detect ants at low abundance that combined hand searching with a high density of baited monitoring stations (12 stations/0.25 ha; HST protocol) was employed within a network of 50 x 50 m cells that subdivided the infestation. During 2016 YCA were found at numerous locations using this method and standard grid-based bait monitoring surveys. Overall, 65 cells where YCA were detected, or cells adjacent to detections, were treated with hydrogel or cat food bait. YCA were not detected during four monitoring events each separated by at least one week, on 85% of these cells after 1–3 treatments, but it was necessary to treat several cells 4–7 times before YCA were eliminated. Results from HST searches allowed us to estimate the probability that YCA were detected when present in an area when searched using that method. Based on this probability, it was determined that areas would have to be searched three times without YCA being detected to allow 93% certainty that the ants were absent. The level of certainty increased to 99% when the search was conducted four times and YCA were not found. Overall, the likelihood of eradicating YCA on Johnston Atoll appears high using existing protocols.

Microfluidic hydrogels for tissue engineering.

PubMed

Huang, Guo You; Zhou, Li Hong; Zhang, Qian Cheng; Chen, Yong Mei; Sun, Wei; Xu, Feng; Lu, Tian Jian

2011-03-01

With advanced properties similar to the native extracellular matrix, hydrogels have found widespread applications in tissue engineering. Hydrogel-based cellular constructs have been successfully developed to engineer different tissues such as skin, cartilage and bladder. Whilst significant advances have been made, it is still challenging to fabricate large and complex functional tissues due mainly to the limited diffusion capability of hydrogels. The integration of microfluidic networks and hydrogels can greatly enhance mass transport in hydrogels and spatiotemporally control the chemical microenvironment of cells, mimicking the function of native microvessels. In this review, we present and discuss recent advances in the fabrication of microfluidic hydrogels from the viewpoint of tissue engineering. Further development of new hydrogels and microengineering technologies will have a great impact on tissue engineering.

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.

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

PubMed

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

2016-12-14

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

Phase-separation induced extraordinary toughening of magnetic hydrogels

NASA Astrophysics Data System (ADS)

Tang, Jingda; Li, Chenghai; Li, Haomin; Lv, Zengyao; Sheng, Hao; Lu, Tongqing; Wang, T. J.

2018-05-01

Phase separation markedly influences the physical properties of hydrogels. Here, we find that poly (N, N-dimethylacrylamide) (PDMA) hydrogels suffer from phase separation in aqueous sodium hydroxide solutions when the concentration is higher than 2 M. The polymer volume fraction and mechanical properties show an abrupt change around the transition point. We utilize this phase separation mechanism to synthesize tough magnetic PDMA hydrogels with the in-situ precipitation method. For comparison, we also prepared magnetic poly (2-acrylamido-2-methyl-propane sulfonic acid sodium) (PNaAMPS) magnetic hydrogels, where no phase separation occurs. The phase-separated magnetic PDMA hydrogels exhibit an extraordinarily high toughness of ˜1000 J m-2; while non-phase-separated magnetic PNaAMPS hydrogels only show a toughness of ˜1 J m-2, three orders of magnitude lower than that of PDMA hydrogels. This phase separation mechanism may become a new approach to prepare tough magnetic hydrogels and inspire more applications.

Enabling Surgical Placement of Hydrogels through Achieving Paste-Like Rheological Behavior in Hydrogel Precursor Solutions

PubMed Central

Beck, Emily C.; Lohman, Brooke L.; Tabakh, Daniel B.; Kieweg, Sarah L.; Gehrke, Stevin H.; Berkland, Cory J.; Detamore, Michael S.

2015-01-01

Hydrogels are a promising class of materials for tissue regeneration, but they lack the ability to be molded into a defect site by a surgeon because hydrogel precursors are liquid solutions that are prone to leaking during placement. Therefore, although the main focus of hydrogel technology and developments are on hydrogels in their crosslinked form, our primary focus is on improving the fluid behavior of hydrogel precursor solutions. In this work, we introduce a method to achieve paste-like hydrogel precursor solutions by combining hyaluronic acid nanoparticles with traditional crosslinked hyaluronic acid hydrogels. Prior to crosslinking, the samples underwent rheological testing to assess yield stress and recovery using linear hyaluronic acid as a control. The experimental groups containing nanoparticles were the only solutions that exhibited a yield stress, demonstrating that the nanoparticulate rather than the linear form of hyaluronic acid was necessary to achieve paste-like behavior. The gels were also photocrosslinked and further characterized as solids, where it was demonstrated that the inclusion of nanoparticles did not adversely affect the compressive modulus and that encapsulated bone marrow-derived mesenchymal stem cells remained viable. Overall, this nanoparticle-based approach provides a platform hydrogel system that exhibits a yield stress prior to crosslinking, and can then be crosslinked into a hydrogel that is capable of encapsulating cells that remain viable. This behavior may hold significant impact for hydrogel applications where a paste-like behavior is desired in the hydrogel precursor solution. PMID:25691398

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.

Silk protein-based hydrogels: Promising advanced materials for biomedical applications.

PubMed

Kapoor, Sonia; Kundu, Subhas C

2016-02-01

Hydrogels are a class of advanced material forms that closely mimic properties of the soft biological tissues. Several polymers have been explored for preparing hydrogels with structural and functional features resembling that of the extracellular matrix. Favourable material properties, biocompatibility and easy processing of silk protein fibers into several forms make it a suitable material for biomedical applications. Hydrogels made from silk proteins have shown a potential in overcoming limitations of hydrogels prepared from conventional polymers. A great deal of effort has been made to control the properties and to integrate novel topographical and functional characteristics in the hydrogel composed from silk proteins. This review provides overview of the advances in silk protein-based hydrogels with a primary emphasis on hydrogels of fibroin. It describes the approaches used to fabricate fibroin hydrogels. Attempts to improve the existing properties or to incorporate new features in the hydrogels by making composites and by improving fibroin properties by genetic engineering approaches are also described. Applications of the fibroin hydrogels in the realms of tissue engineering and controlled release are reviewed and their future potentials are discussed. This review describes the potentiality of silk fibroin hydrogel. Silk Fibroin has been widely recognized as an interesting biomaterial. Due to its properties including high mechanical strength and excellent biocompatibility, it has gained wide attention. Several groups are exploring silk-based materials including films, hydrogels, nanofibers and nanoparticles for different biomedical applications. Although there is a good amount of literature available on general properties and applications of silk based biomaterials, there is an inadequacy of extensive review articles that specifically focus on silk based hydrogels. Silk-based hydrogels have a strong potential to be utilized in biomedical applications. Our work is an effort to highlight the research that has been done in the area of silk-based hydrogels. It aims to provide an overview of the advances that have been made and the future course available. It will provide an overview of the silk-based hydrogels as well as may direct the readers to the specific areas of application. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Feasibility of hydrogel fiducial markers for in vivo proton range verification using PET

NASA Astrophysics Data System (ADS)

Cho, Jongmin; Campbell, Patrick; Wang, Min; Alqathami, Mamdooh; Mawlawi, Osama; Kerr, Matthew; Cho, Sang Hyun

2016-03-01

Biocompatible/biodegradable hydrogel polymers were immersed in 18O-enriched water and 16O-water to create 18O-water hydrogels and 16O-water hydrogels. In both cases, the hydrogels were made of ~91 wt% water and ~9 wt% polymer. In addition, 5-8 μm Zn powder was suspended in 16O-water and 18O-enriched water and cross-linked with hydrogel polymers to create Zn/16O-water hydrogels (30/70 wt%, ~9 wt% polymer) and Zn/18O-water hydrogels (10/90 wt%), respectively. A block of extra-firm ‘wet’ tofu (12.3  ×  8.8  ×  4.9 cm, ρ  ≈  1.05 g cm-3) immersed in water was injected with Zn/16O-water hydrogels (0.9 ml each) at four different depths using an 18-gauge needle. Similarly, Zn/18O-water hydrogels (0.9 ml) were injected into a second tofu phantom. As a reference, both 16O-water hydrogels (1.8 ml) and 18O-water hydrogels (0.9 ml) in Petri dishes were irradiated in a ‘dry’ environment. The hydrogels in the wet tofu phantoms and dry Petri dishes were scanned via CT and images were used for treatment planning. Then, they were positioned at the proton distal dose fall-off region and irradiated (2 Gy) followed by PET/CT imaging. Notably high PET signals were observed only in 18O-water hydrogels in the dry environment. The visibility of the Zn/16O-water hydrogels injected into the tofu phantom was outstanding in CT images, but these hydrogels provided no noticeable PET signals. The visibility of the Zn/18O-water hydrogels in the wet tofu were excellent on CT and moderate on PET; however, the PET signals were weaker than those in the dry environment, possibly owing to 18O-water leaching out. The hydrogel markers studied here could be used to develop universal PET/CT fiducial markers. Their PET visibility (attributed more to activated 18O-water than Zn) after proton irradiation can be used for proton therapy/range verification. More investigation is needed to slow down the leaching of 18O-water.

Visible light induced electropolymerization of suspended hydrogel bioscaffolds in a microfluidic chip.

PubMed

Li, Pan; Yu, Haibo; Liu, Na; Wang, Feifei; Lee, Gwo-Bin; Wang, Yuechao; Liu, Lianqing; Li, Wen Jung

2018-05-23

The development of microengineered hydrogels co-cultured with cells in vitro could advance in vivo bio-systems in both structural complexity and functional hierarchy, which holds great promise for applications in regenerative tissues or organs, drug discovery and screening, and bio-sensors or bio-actuators. Traditional hydrogel microfabrication technologies such as ultraviolet (UV) laser or multiphoton laser stereolithography and three-dimensional (3D) printing systems have advanced the development of 3D hydrogel micro-structures but need either expensive and complex equipment, or harsh material selection with limited photoinitiators. Herein, we propose a simple and flexible hydrogel microfabrication method based on a ubiquitous visible-light projection system combined with a custom-designed photosensitive microfluidic chip, to rapidly (typically several to tens of seconds) fabricate various two-dimensional (2D) hydrogel patterns and 3D hydrogel constructs. A theoretical layer-by-layer model that involves continuous polymerizing-delaminating-polymerizing cycles is presented to explain the polymerization and structural formation mechanism of hydrogels. A large area of hydrogel patterns was efficiently fabricated without the usage of costly laser systems or photoinitiators, i.e., a stereoscopic mesh-like hydrogel network with intersecting hydrogel micro-belts was fabricated via a series of dynamic-changing digital light projections. The pores and gaps of the hydrogel network are tunable, which facilitates the supply of nutrients and discharge of waste in the construction of 3D thick bio-models. Cell co-culture experiments showed the effective regulation of cell spreading by hydrogel scaffolds fabricated by the new method presented here. This visible light enabled hydrogel microfabrication method may provide new prospects for designing cell-based units for advanced biomedical studies, e.g., for 3D bio-models or bio-actuators in the future.

Nanostructured PEG-based hydrogels with tunable physical properties for gene delivery to human mesenchymal stem cells.

PubMed

Li, Yan; Yang, Chuan; Khan, Majad; Liu, Shaoqiong; Hedrick, James L; Yang, Yi-Yan; Ee, Pui-Lai R

2012-09-01

Effective delivery of DNA to direct cell behavior in a well defined three dimensional scaffold offers a superior approach in tissue engineering. In this study, we synthesized biodegradable nanostructured hydrogels with tunable physical properties for cell and gene delivery. The hydrogels were formed via Michael addition chemistry by reacting a four-arm acrylate-terminated PEG with a four-arm thiol-functionalized PEG. Nanosized micelles self-assembled from the amphiphilic PEG-b-polycarbonate diblock copolymer, having reactive end-groups, were chemically incorporated into the hydrogel networks at various contents. The use of Michael addition chemistry allows for in situ hydrogel formation under the physiological conditions. Mechanical property analysis of the hydrogels revealed a correlation between the content of micelles and the storage modulus of the hydrogels. Internal morphology of hydrogels was observed using a field emission scanning electron microscope, which showed that the number and/or size of the pores in the hydrogel increased with increasing micelle content due to reduced crosslinking degree. There exists an optimal micelle content for cell proliferation and gene transfection. MTT assays demonstrated the highest cell viability in the hydrogel with 20% micelles. The gene expression level in hMSCs in the hydrogel with 20% micelles was also significantly higher than that in the hydrogel without micelles. The enhanced cell viability and gene expression in the hydrogel with the optimized micelle content are likely attributed to the physical properties that provide a better environment for cell-matrix interactions. Therefore, incorporating micelles into the hydrogel is a good strategy to control cellular behavior in 3-D through changes in physical properties of the microenvironment. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

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

2013-01-01

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

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

PubMed Central

Sun, Xiuzhi S.; Nguyen, Thu A.

2013-01-01

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

Non-invasive monitoring of in vivo hydrogel degradation and cartilage regeneration by multiparametric MR imaging

PubMed Central

Chen, Zelong; Yan, Chenggong; Yan, Shina; Liu, Qin; Hou, Meirong; Xu, Yikai; Guo, Rui

2018-01-01

Numerous biodegradable hydrogels for cartilage regeneration have been widely used in the field of tissue engineering. However, to non-invasively monitor hydrogel degradation and efficiently evaluate cartilage restoration in situ is still challenging. Methods: A ultrasmall superparamagnetic iron oxide (USPIO)-labeled cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was developed to monitor hydrogel degradation during cartilage regeneration. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogel degradation and cartilage regeneration of different implants were assessed using multiparametric magnetic resonance imaging (MRI) and further confirmed by histological analysis in a rabbit cartilage defect model for 3 months. Results: USPIO-labeled hydrogels showed sufficient MR contrast enhancement and retained stability without loss of the relaxation rate. Neither the mechanical properties of the hydrogels nor the proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by USPIO labeling in vitro. CNC/SF hydrogels with BMSCs degraded more quickly than the acellular hydrogels as reflected by the MR relaxation rate trends in vivo. The morphology of neocartilage was noninvasively visualized by the three-dimensional water-selective cartilage MRI scan sequence, and the cartilage repair was further demonstrated by macroscopic and histological observations. Conclusion: This USPIO-labeled CNC/SF hydrogel system provides a new perspective on image-guided tissue engineering for cartilage regeneration. PMID:29464005

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

PubMed

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

2018-05-15

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

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2017-09-29

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

Characterization of human adipose tissue-derived stem cells in vitro culture and in vivo differentiation in a temperature-sensitive chitosan/β- glycerophosphate/collagen hybrid hydrogel.

PubMed

Song, Kedong; Li, Liying; Yan, Xinyu; Zhang, Wen; Zhang, Yu; Wang, Yiwei; Liu, Tianqing

2017-01-01

In this study, the interaction of human adipose tissue-derived stem cells (ADSCs) with chitosan/β-glycerophosphate/collagen (C/GP/Co) hybrid hydrogel was test, followed by investigating the capability of engineered adipose tissue formation using this ADSCs seeded hydrogel. The ADSCs were harvested and mixed with a C/GP/Co hydrogel followed by a gelation at 37°C and an in vitro culture. The results showed that the ADSCs within C/GP/Co hydrogels achieved a 30% of expansion over 7days in culture medium and encapsulated cell in C/GP/Co hydrogel demonstrated a characteristic morphology with high viability over 5days. C/GP/Co hydrogel were subcutaneous injected into SD-rats to assess the biocompatibility. The induced ADSCs-C/GP/Co hydrogel and non-induced ADSCs-C/GP/Co hydrogel were subcutaneously injected into nude mice for detecting potential of adipogenic differentiation. It has shown that C/GP/Co hydrogel were well tolerated in SD rats where they had persisted over 4weeks post implantation. Histology analysis indicated that induced ADSCs-C/GP/Co hydrogel has a greater number of adipocytes and vascularized adipose tissues compared with non-induced ADSCs-C/GP/Co hydrogel. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

A robust, highly stretchable supramolecular polymer conductive hydrogel with self-healability and thermo-processability

NASA Astrophysics Data System (ADS)

Wu, Qian; Wei, Junjie; Xu, Bing; Liu, Xinhua; Wang, Hongbo; Wang, Wei; Wang, Qigang; Liu, Wenguang

2017-01-01

Dual amide hydrogen bond crosslinked and strengthened high strength supramolecular polymer conductive hydrogels were fabricated by simply in situ doping poly (N-acryloyl glycinamide-co-2-acrylamide-2-methylpropanesulfonic) (PNAGA-PAMPS) hydrogels with PEDOT/PSS. The nonswellable conductive hydrogels in PBS demonstrated high mechanical performances—0.22-0.58 MPa tensile strength, 1.02-7.62 MPa compressive strength, and 817-1709% breaking strain. The doping of PEDOT/PSS could significantly improve the specific conductivities of the hydrogels. Cyclic heating and cooling could lead to reversible sol-gel transition and self-healability due to the dynamic breakup and reconstruction of hydrogen bonds. The mending hydrogels recovered not only the mechanical properties, but also conductivities very well. These supramolecular conductive hydrogels could be designed into arbitrary shapes with 3D printing technique, and further, printable electrode can be obtained by blending activated charcoal powder with PNAGA-PAMPS/PEDOT/PSS hydrogel under melting state. The fabricated supercapacitor via the conducting hydrogel electrodes possessed high capacitive performances. These cytocompatible conductive hydrogels have a great potential to be used as electro-active and electrical biomaterials.

Photopolymerizable chitosan-collagen hydrogels for bone tissue engineering.

PubMed

Arakawa, Christopher; Ng, Ronald; Tan, Steven; Kim, Soyon; Wu, Benjamin; Lee, Min

2017-01-01

Photopolymerizable hydrogels derived from naturally occurring polymers have attracted significant interest in tissue-engineering applications due to their excellent biocompatibility, hydrophilic nature favourable for cell ingrowth and ability to be cured in situ through a minimally invasive procedure. In this study, we developed a composite hydrogel consisting of photocrosslinkable methacrylated glycol chitosan (MeGC) and semi-interpenetrating collagen (Col) with a riboflavin photoinitiator under blue light. The incorporation of Col in MeGC hydrogels enhanced the compressive modulus and slowed the degradation rate of the hydrogels. MeGC-Col composite hydrogels significantly enhanced cellular attachment, spreading, proliferation and osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) seeded on the hydrogels compared with pure MeGC hydrogels, as observed by upregulated alkaline phosphatase (ALP) activity as well as increased mineralization. Similarly, when cells were encapsulated within hydrogels, BMSCs exhibited greater proliferation, ALP activity and mineral deposits in the presence of Col. These findings demonstrate that MeGC-Col composite hydrogels may be useful in promoting bone regeneration. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

A protocol for rheological characterization of hydrogels for tissue engineering strategies.

PubMed

Zuidema, Jonathan M; Rivet, Christopher J; Gilbert, Ryan J; Morrison, Faith A

2014-07-01

Hydrogels are studied extensively for many tissue engineering applications, and their mechanical properties influence both cellular and tissue compatibility. However, it is difficult to compare the mechanical properties of hydrogels between studies due to a lack of continuity between rheological protocols. This study outlines a straightforward protocol to accurately determine hydrogel equilibrium modulus and gelation time using a series of rheological tests. These protocols are applied to several hydrogel systems used within tissue engineering applications: agarose, collagen, fibrin, Matrigel™, and methylcellulose. The protocol is outlined in four steps: (1) Time sweep to determine the gelation time of the hydrogel. (2) Strain sweep to determine the linear-viscoelastic region of the hydrogel with respect to strain. (3) Frequency sweep to determine the linear equilibrium modulus plateau of the hydrogel. (4) Time sweep with values obtained from strain and frequency sweeps to accurately report the equilibrium moduli and gelation time. Finally, the rheological characterization protocol was evaluated using a composite Matrigel™-methylcellulose hydrogel blend whose mechanical properties were previously unknown. The protocol described herein provides a standardized approach for proper analysis of hydrogel rheological properties. © 2013 Wiley Periodicals, Inc.

A review of gradient stiffness hydrogels used in tissue engineering and regenerative medicine.

PubMed

Xia, Tingting; Liu, Wanqian; Yang, Li

2017-06-01

Substrate stiffness is known to impact characteristics including cell differentiation, proliferation, migration and apoptosis. Hydrogels are polymeric materials distinguished by high water content and diverse physical properties. Gradient stiffness hydrogels are designed by the need to develop biologically friendly materials as extracellular matrix (ECM) alternatives to replace the separated and narrow-ranged hydrogel substrates. Important new discoveries in cell behaviors have been realized with model gradient stiffness hydrogel systems from the two-dimensional (2D) to three-dimensional (3D) scale. Basic and clinical applications for gradient stiffness hydrogels in tissue engineering and regenerative medicine continue to drive the development of stiffness and structure varied hydrogels. Given the importance of gradient stiffness hydrogels in basic research and biomedical applications, there is a clear need for systems for gradient stiffness hydrogel design strategies and their applications. This review will highlight past work in the field of gradient stiffness hydrogels fabrication methods, mechanical property test, applications as well as areas for future study. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1799-1812, 2017. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2017-05-10

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

Engineering ellipsoidal cap-like hydrogel particles as building blocks or sacrificial templates for three-dimensional cell culture.

PubMed

Zhang, Weiwei; Huang, Guoyou; Ng, Kelvin; Ji, Yuan; Gao, Bin; Huang, Liqing; Zhou, Jinxiong; Lu, Tian Jian; Xu, Feng

2018-03-26

Hydrogel particles that can be engineered to compartmentally culture cells in a three-dimensional (3D) and high-throughput manner have attracted increasing interest in the biomedical area. However, the ability to generate hydrogel particles with specially designed structures and their potential biomedical applications need to be further explored. This work introduces a method for fabricating hydrogel particles in an ellipsoidal cap-like shape (i.e., ellipsoidal cap-like hydrogel particles) by employing an open-pore anodic aluminum oxide membrane. Hydrogel particles of different sizes are fabricated. The ability to produce ellipsoidal cap-like magnetic hydrogel particles with controlled distribution of magnetic nanoparticles is demonstrated. Encapsulated cells show high viability, indicating the potential for using these hydrogel particles as structure- and remote-controllable building blocks for tissue engineering application. Moreover, the hydrogel particles are also used as sacrificial templates for fabricating ellipsoidal cap-like concave wells, which are further applied for producing size controllable cell aggregates. The results are beneficial for the development of hydrogel particles and their applications in 3D cell culture.

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

NASA Astrophysics Data System (ADS)

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

2013-08-01

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

[Thromboresistance of glucose-containing hydrogels].

PubMed

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

2013-01-01

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

Femtosecond UV-laser pulses to unveil protein-protein interactions in living cells.

PubMed

Itri, Francesco; Monti, Daria M; Della Ventura, Bartolomeo; Vinciguerra, Roberto; Chino, Marco; Gesuele, Felice; Lombardi, Angelina; Velotta, Raffaele; Altucci, Carlo; Birolo, Leila; Piccoli, Renata; Arciello, Angela

2016-02-01

A hallmark to decipher bioprocesses is to characterize protein-protein interactions in living cells. To do this, the development of innovative methodologies, which do not alter proteins and their natural environment, is particularly needed. Here, we report a method (LUCK, Laser UV Cross-linKing) to in vivo cross-link proteins by UV-laser irradiation of living cells. Upon irradiation of HeLa cells under controlled conditions, cross-linked products of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were detected, whose yield was found to be a linear function of the total irradiation energy. We demonstrated that stable dimers of GAPDH were formed through intersubunit cross-linking, as also observed when the pure protein was irradiated by UV-laser in vitro. We proposed a defined patch of aromatic residues located at the enzyme subunit interface as the cross-linking sites involved in dimer formation. Hence, by this technique, UV-laser is able to photofix protein surfaces that come in direct contact. Due to the ultra-short time scale of UV-laser-induced cross-linking, this technique could be extended to weld even transient protein interactions in their native context.

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

Effect of Broadband Nature of Marine Mammal Echolocation Clicks on Click-Based Population Density Estimates

DTIC Science & Technology

2015-09-30

Blainville’s beaked whales (Mesoplodon densirostris), known to be sensitive to sonar sound and therefore of high relevance to the US Navy, and sperm whale...this study were obtained from von Benda-Beckmann et al. (2010) for the beaked whale, and Zimmer (2011) for the sperm whale. 4 For background...Blainville’s beaked whales and sperm whales are commonly present. Analysis of the noise levels on the system indicated that the background noise was system

Modification of the explant system for the removal of well fixed hip resurfacing sockets.

PubMed

Rawal, Jaikirty S; Soler, J Agustin; Rhee, Jae S; Dobson, Michael H; Konan, Sujith; Haddad, Fares S

2010-10-01

A major concern during revision hip arthroplasty is acetabular bone loss during the extraction of well-fixed acetabular components. Despite the good early survivorship of resurfacing prostheses, revision surgery may be necessary. We recommend the use of the Explant acetabular extraction system (Zimmer, Warsaw, Ind) with a trial liner to preserve acetabular bone stock. We present 2 cases of revised resurfacings using this technique, demonstrating minimal interference to the remaining acetabular bone. Copyright © 2010 Elsevier Inc. All rights reserved.

Buffer Loading and Chunking in Sequential Keypressing (Het Laden van de Motor Buffer Versus Het Gebruik van Motor Chunks bij Sequentieule Toetsdrukseries)

DTIC Science & Technology

1994-03-18

Paillard, 1960). The benefit of movement chunks would lie in the associated reduction of storage and retrieval capacity (see e.g. Gallistel , 1980; Jones...1983; Fromkin, 1981; Gallistel , 1980; Zimmer & Korndle, 1988) but interval durations should be affected as well. The notion of sequence-specific...point where they can be made more rapidly and accurately with little variation. Then they become welded together into ’chunks’" ( Gallistel , 1980, p.367

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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Designing degradable hydrogels for orthogonal control of cell microenvironments

PubMed Central

Kharkar, Prathamesh M.

2013-01-01

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

Viscoelastic and fractal characteristics of a supramolecular hydrogel hybridized with clay nanoparticles.

PubMed

Song, Fei; Zhang, Li-Ming; Shi, Jun-Feng; Li, Nan-Nan

2010-12-01

The supramolecular hydrogels derived from low-molecular-mass gelators represent a unique class of soft matters and have important potential applications in biomedical fields, separation technology and cosmetic science. However, they suffer usually from weak mechanical and viscoelastic properties. In this work, we carry out the in situ hybridization of clay nanoparticles (Laponite RD) into the supramolecular hydrogel formed from a low-molecular-mass hydrogelator, 2,6-di[N-(carboxyethyl carbonyl)amino]pyridine (DAP), and investigate the viscoelastic and structural characteristics of resultant hybrid hydrogel. It was found that a small concentration of Laponite RD could lead to a significant increase in the storage modulus, loss modulus or complex viscosity. Compared with neat DAP hydrogel, the hybrid hydrogel has a greater hydrogel strength and a lower relaxation exponent. In particular, the enhancement of the clay nanoparticles to the viscoelastic properties of the DAP hydrogel is more effective in the case of higher DAP concentration. By relating its macroscopic elastic properties to a scaling fractal model, such a hybrid hydrogel was confirmed to be in the strong-link regime and to have a more complex network structure with a higher fractal dimension when compared with neat DAP hydrogel. Copyright © 2010 Elsevier B.V. All rights reserved.

Reinforcement of mono- and bi-layer poly(ethylene glycol) hydrogels with a fibrous collagen scaffold

PubMed Central

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

2015-01-01

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 bilayer, multi-phase hydrogel interpenetrated with a fibrous collagen scaffold. ‘Soft’ 10% (w/w) and ‘stiff’ 30% (w/w) PEGDM was formed into mono- or bilayer 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 >500μm into the soft layer). Including a fibrous scaffold into both soft and stiff single-phase hydrogels significantly increased tangent modulus and toughness and decreased lateral expansion under compressive loading. In multi-phase hydrogels, finite element simulations predict substantially reduced stress and strain gradients across the soft—stiff hydrogel interface. When combining two low moduli constituent material, 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

High performances of dual network PVA hydrogel modified by PVP using borax as the structure-forming accelerator

PubMed Central

Huang, Min; Hou, Yi; Li, Yubao; Wang, Danqing; Zhang, Li

2017-01-01

Abstract A dual network hydrogel made up of polyvinylalcohol (PVA) crosslinked by borax and polyvinylpyrrolidone (PVP) was prepared by means of freezing-thawing circles. Here PVP was incorporated by linking with PVA to form a network structure, while the introduction of borax played the role of crosslinking PVA chains to accelerate the formation of a dual network structure in PVA/PVP composite hydrogel, thus endowing the hydrogel with high mechanical properties. The effects of both PVP and borax on the hydrogels were evaluated by comparing the two systems of PVA/PVP/borax and PVA/borax hydrogels. In the former system, adding 4.0% PVP not only increased the water content and the storage modulus but also enhanced the mechanical strength of the final hydrogel. But an overdose of PVP just as more than 4.0% tended to undermine the structure of hydrogels, and thus deteriorated hydrogels’ properties because of the weakened secondary interaction between PVP and PVA. Likewise, increasing borax could promote the gel crosslinking degree, thus making gels show a decrease in water content and swelling ratio, meanwhile shrinking the pores inside the hydrogels and finally enhancing the mechanical strength of hydrogels prominently. The developed hydrogel with high performances holds great potential for applications in biomedical and industrial fields. PMID:29491822

Mechanical properties, structure, bioadhesion, and biocompatibility of pectin hydrogels.

PubMed

Markov, Pavel A; Krachkovsky, Nikita S; Durnev, Eugene A; Martinson, Ekaterina A; Litvinets, Sergey G; Popov, Sergey V

2017-09-01

The surface structure, biocompatibility, textural, and adhesive properties of calcium hydrogels derived from 1, 2, and 4% solutions of apple pectin were examined in this study. An increase in the pectin concentration in hydrogels was shown to improve their stability toward elastic and plastic deformation. The elasticity of pectin hydrogels, measured as Young's modulus, ranged from 6 to 100 kPa. The mechanical properties of the pectin hydrogels were shown to correspond to those of soft tissues. The characterization of surface roughness in terms of the roughness profile (Ra) and the root-mean-square deviation of the roughness profile (Rq) indicated an increased roughness profile for hydrogels depending on their pectin concentration. The adhesion of AU2% and AU4% hydrogels to the serosa abdominal wall, liver, and colon was higher than that of the AU1% hydrogel. The adhesion of macrophages and the non-specific adsorption of blood plasma proteins were found to increase as the pectin concentration in the hydrogels increased. The rate of degradation of all hydrogels was higher in phosphate buffered saline (PBS) than that in DMEM and a fibroblast cell monolayer. The pectin hydrogel was also found to have a low cytotoxicity. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2572-2581, 2017. © 2017 Wiley Periodicals, Inc.

3D-Hydrogel Based Polymeric Nanoreactors for Silver Nano-Antimicrobial Composites Generation.

PubMed

Soto-Quintero, Albanelly; Romo-Uribe, Ángel; Bermúdez-Morales, Víctor H; Quijada-Garrido, Isabel; Guarrotxena, Nekane

2017-08-01

This study underscores the development of Ag hydrogel nanocomposites, as smart substrates for antibacterial uses, via innovative in situ reactive and reduction pathways. To this end, two different synthetic strategies were used. Firstly thiol-acrylate (PSA) based hydrogels were attained via thiol-ene and radical polymerization of polyethylene glycol (PEG) and polycaprolactone (PCL). As a second approach, polyurethane (PU) based hydrogels were achieved by condensation polymerization from diisocyanates and PCL and PEG diols. In fact, these syntheses rendered active three-dimensional (3D) hydrogel matrices which were used as nanoreactors for in situ reduction of AgNO₃ to silver nanoparticles. A redox chemistry of stannous catalyst in PU hydrogel yielded spherical AgNPs formation, even at 4 °C in the absence of external reductant; and an appropriate thiol-functionalized polymeric network promoted spherical AgNPs well dispersed through PSA hydrogel network, after heating up the swollen hydrogel at 103 °C in the presence of citrate-reductant. Optical and swelling behaviors of both series of hydrogel nanocomposites were investigated as key factors involved in their antimicrobial efficacy over time. Lastly, in vitro antibacterial activity of Ag loaded hydrogels exposed to Pseudomona aeruginosa and Escherichia coli strains indicated a noticeable sustained inhibitory effect, especially for Ag-PU hydrogel nanocomposites with bacterial inhibition growth capabilities up to 120 h cultivation.

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

PubMed

Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2014-07-01

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

Three-Dimensional Bioprinting of Oppositely Charged Hydrogels with Super Strong Interface Bonding.

PubMed

Li, Huijun; Tan, Yu Jun; Liu, Sijun; Li, Lin

2018-04-04

A novel strategy to improve the adhesion between printed layers of three-dimensional (3D) printed constructs is developed by exploiting the interaction between two oppositely charged hydrogels. Three anionic hydrogels [alginate, xanthan, and κ-carrageenan (Kca)] and three cationic hydrogels [chitosan, gelatin, and gelatin methacrylate (GelMA)] are chosen to find the optimal combination of two oppositely charged hydrogels for the best 3D printability with strong interface bonding. Rheological properties and printability of the hydrogels, as well as structural integrity of printed constructs in cell culture medium, are studied as functions of polymer concentration and the combination of hydrogels. Kca2 (2 wt % Kca hydrogel) and GelMA10 (10 wt % GelMA hydrogel) are found to be the best combination of oppositely charged hydrogels for 3D printing. The interfacial bonding between a Kca layer and a GelMA layer is proven to be significantly higher than that of the bilayered Kca or bilayered GelMA because of the formation of polyelectrolyte complexes between the oppositely charged hydrogels. A good cell viability of >96% is obtained for the 3D-bioprinted Kca-GelMA construct. This novel strategy has a great potential for 3D bioprinting of layered constructs with a strong interface bonding.

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

PubMed Central

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

2018-01-01

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

Reinforcing the inner phase of the filled hydrogels with CNTs alters drug release properties and human keratinocyte morphology: A study on the gelatin- tamarind gum filled hydrogels.

PubMed

Maharana, Vivek; Gaur, Deepanjali; Nayak, Suraj K; Singh, Vinay K; Chakraborty, Subhabrata; Banerjee, Indranil; Ray, Sirsendu S; Anis, Arfat; Pal, Kunal

2017-11-01

The study reports the synthesis and characterization of gelatin-tamarind gum (TG) based filled hydrogels for drug delivery applications. In this study, three different types of carbon nanotubes (CNTs) were incorporated within the dispersed TG phase of the filled hydrogels. The prepared hydrogels were thoroughly characterised using bright field microscope, FESEM, FTIR spectroscopy, differential scanning calorimeter, and mechanical tester. The swelling and the drug (salicylic acid) release properties of the filled hydrogels were also evaluated. The micrographs revealed the formation of biphasic systems. The internal phase appeared as agglomerates, and the CNTs were confined within the dispersed TG phase. FTIR and XRD studies revealed that CNTs promoted associative interactions among the components of the hydrogel, which promoted the formation of large crystallite size. The mechanical study indicated better resistance to the breakdown of the architecture of the CNT-containing filled hydrogels. Drug release studies, both passive and iontophoretic, suggested that the non-Fickian diffusion of the drug was prevalent during its release from hydrogel matrices. The prepared hydrogels were cytocompatible with human keratinocytes. The results suggested the probable use of such hydrogels in wound healing, tissue engineering and drug delivery applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tough Hydrogel Robots: High-Speed, High-Force and Opto-sonically Invisible in Water

NASA Astrophysics Data System (ADS)

Zhao, Xuanhe

Sea animals such as leptocephali develop tissues and organs composed of active transparent hydrogels to achieve agile motions and natural camouflage in water. Hydrogel-based actuators that can imitate the capabilities of leptocephali will enable new applications in diverse fields. However, existing hydrogel actuators, mostly osmotic-driven, are intrinsically low-speed and/or low-force; and their camouflage capabilities have not been explored. Here we show that hydraulic actuations of tough hydrogels with designed structures and properties can give soft actuators and robots that are high-speed, high-force, and optically and sonically camouflaged in water. We invent a simple method capable of assembling physically-crosslinked hydrogel parts followed by covalent crosslinking to fabricate large-scale hydraulic hydrogel actuators and robots with robust bodies and interfaces. The hydrogel actuators and robots can maintain their robustness and functionality over multiple cycles of actuations, owning to the anti-fatigue property of the hydrogel under moderate stresses. A multiscale theoretical framework has been developed to guide the design and optimization of the hydrogel robots. We further demonstrate that the agile and transparent hydrogel actuators and robots perform extraordinary functions including swimming, kicking rubber-balls and catching a live fish in water. The work was supported by NSF(No. CMMI- 1253495) and ONR (No. N00014-14-1-0528).

Mechanical characteristics of beta sheet-forming peptide hydrogels are dependent on peptide sequence, concentration and buffer composition

PubMed Central

Müller, Michael; König, Finja; Meyer, Nina; Gattlen, Jasmin; Pieles, Uwe; Peters, Kirsten; Kreikemeyer, Bernd; Mathes, Stephanie; Saxer, Sina

2018-01-01

Self-assembling peptide hydrogels can be modified regarding their biodegradability, their chemical and mechanical properties and their nanofibrillar structure. Thus, self-assembling peptide hydrogels might be suitable scaffolds for regenerative therapies and tissue engineering. Owing to the use of various peptide concentrations and buffer compositions, the self-assembling peptide hydrogels might be influenced regarding their mechanical characteristics. Therefore, the mechanical properties and stability of a set of self-assembling peptide hydrogels, consisting of 11 amino acids, made from four beta sheet self-assembling peptides in various peptide concentrations and buffer compositions were studied. The formed self-assembling peptide hydrogels exhibited stiffnesses ranging from 0.6 to 205 kPa. The hydrogel stiffness was mostly affected by peptide sequence followed by peptide concentration and buffer composition. All self-assembling peptide hydrogels examined provided a nanofibrillar network formation. A maximum self-assembling peptide hydrogel dissolution of 20% was observed for different buffer solutions after 7 days. The stability regarding enzymatic and bacterial digestion showed less degradation in comparison to the self-assembling peptide hydrogel dissolution rate in buffer. The tested set of self-assembling peptide hydrogels were able to form stable scaffolds and provided a broad spectrum of tissue-specific stiffnesses that are suitable for a regenerative therapy. PMID:29657766

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

PubMed

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

2014-07-17

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

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

PubMed

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

2018-02-01

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

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

PubMed

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

2018-05-01

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

Polymeric hydrogels for novel contact lens-based ophthalmic drug delivery systems: a review.

PubMed

Xinming, Li; Yingde, Cui; Lloyd, Andrew W; Mikhalovsky, Sergey V; Sandeman, Susan R; Howel, Carol A; Liewen, Liao

2008-04-01

Only about 5% of drugs administrated by eye drops are bioavailable, and currently eye drops account for more than 90% of all ophthalmic formulations. The bioavailability of ophthalmic drugs can be improved by a soft contact lens-based ophthalmic drug delivery system. Several polymeric hydrogels have been investigated for soft contact lens-based ophthalmic drug delivery systems: (i) polymeric hydrogels for conventional contact lens to absorb and release ophthalmic drugs; (ii) polymeric hydrogels for piggyback contact lens combining with a drug plate or drug solution; (iii) surface-modified polymeric hydrogels to immobilize drugs on the surface of contact lenses; (iv) polymeric hydrogels for inclusion of drugs in a colloidal structure dispersed in the lens; (v) ion ligand-containing polymeric hydrogels; (vi) molecularly imprinted polymeric hydrogels which provide the contact lens with a high affinity and selectivity for a given drug. Polymeric hydrogels for these contact lens-based ophthalmic drug delivery systems, their advantages and drawbacks are critically analyzed in this review.

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

Efficient adsorption of Au(CN)2- from gold cyanidation with graphene oxide-polyethylenimine hydrogel as adsorbent

NASA Astrophysics Data System (ADS)

Yang, Lang; Jia, Feifei; Yang, Bingqiao; Song, Shaoxian

The adsorption of gold cyanide complex ion (Au(CN)2-) on graphene oxide-polyethylenimine hydrogel (GO/PEI hydrogel) from gold cyanidation has been studied to explore the possibility of the application of GO/PEI hydrogel in gold cyanidation process for extracting gold from ores. The adsorption was carried out in artificial Au(CN)2- aqueous solution with GO/PEI hydrogel as adsorbent. The experimental results, as well as IR, XPS and SEM-EDS, have shown that GO/PEI hydrogel exhibited a high adsorption capacity and a fast adsorption rate of Au(CN)2-, suggesting that GO/PEI hydrogel might be a good adsorbent for the recovery of Au(CN)2-. The adsorption of Au(CN)2- on GO/PEI hydrogel obeyed the Langmuir isotherm model and fitted well with the pseudo second order model. The good recovery of Au(CN)2- was largely related to the porous structure, large specific surface area, as well as the oxygenous functional groups on the surface of GO/PEI hydrogel.

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

PubMed

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

2017-11-01

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

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

PubMed Central

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

2012-01-01

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

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. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

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

2010-11-01

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

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

PubMed

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

2017-06-01

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

Soft poly(2-chloroaniline)/pectin hydrogel and its electromechanical properties.

PubMed

Kongkaew, Wanar; Sangwan, Watchara; Lerdwijitjarud, Wanchai; Sirivat, Anuvat

2018-01-01

Pectin hydrogels were successfully fabricated with various physical crosslinkers and concentrations for soft actuator applications. A small amount of synthesized P2ClAn was added as a dispersed phase into the pectin matrix. The electromechanical properties of the pectin hydrogels and blends were investigated under the effects of electric field strength, ionic crosslinker type and concentration, and P2ClAn concentration. The electromechanical properties of the pectin hydrogel as crosslinked by Fe 2+ were superior to other pectin hydrogels. The pristine pectin hydrogel and the P2ClAn/Pectin hydrogel blended with 0.10%v/v P2ClAn provided the high storage modulus sensitivity values of 8.61 and 14.01, respectively, under the electric field strength of 800 V/mm. The P2ClAn/Pectin hydrogel blend responded to the electric field with higher dielectrophoretic forces, but lower deflections relative to the pristine pectin hydrogel due to the additional P2ClAn polarization and the latter lower rigidity.

Preparation and characterization of oil palm frond based cellulose hydrogel and its swelling properties

NASA Astrophysics Data System (ADS)

Selvakumaran, Nesha; Lazim, Mohd Azwani Shah bin Mat

2016-11-01

Malaysia is one of the largest producer of palm oil thus the quantity of biomass each year from this industry is very large. The oil palm frond from palm oil industry can be used as a source of cellulose which can be incorporated into hydrogel to be used as adsorbent. This research reported how to disperse 2 % cellulose in a `green-solution' prepared by using urea and sodium hydroxide. Polymerization is carried out between the monomers polyacrylamide and cellulose using microwave to form hydrogel. Hydrogel with 2 % cellulose have a swelling index of 1814 %. Meanwhile, zero hydrogel which is made with only polyacrylamide has swelling index of 15 %. Scanning electron microscope shows that cellulose hydrogel have a rough surface compared with zero hydrogel. This might attribute to the high swelling index for cellulose hydrogel compared with zero hydrogel. Meanwhile, FTIR shows that successful polymerization has occurred between polyacrylamide and cellulose with the characteristic band at 1657.99 cm-1 which is for N-H bond.

Distributed vasculogenesis from modular agarose-hydroxyapatite-fibrinogen microbeads.

PubMed

Rioja, Ana Y; Daley, Ethan L H; Habif, Julia C; Putnam, Andrew J; Stegemann, Jan P

2017-06-01

Critical limb ischemia impairs circulation to the extremities, causing pain, disrupted wound healing, and potential tissue necrosis. Therapeutic angiogenesis seeks to repair the damaged microvasculature directly to restore blood flow. In this study, we developed modular, micro-scale constructs designed to possess robust handling qualities, allow in vitro pre-culture, and promote microvasculature formation. The microbead matrix consisted of an agarose (AG) base to prevent aggregation, combined with cell-adhesive components of fibrinogen (FGN) and/or hydroxyapatite (HA). Microbeads encapsulating a co-culture of human umbilical vein endothelial cells (HUVEC) and fibroblasts were prepared and characterized. Microbeads were generally 80-100µm in diameter, and the size increased with the addition of FGN and HA. Addition of HA increased the yield of microbeads, as well as the homogeneity of distribution of FGN within the matrix. Cell viability was high in all microbead types. When cell-seeded microbeads were embedded in fibrin hydrogels, HUVEC sprouting and inosculation between neighboring microbeads were observed over seven days. Pre-culture of microbeads for an additional seven days prior to embedding in fibrin resulted in significantly greater HUVEC network length in AG+HA+FGN microbeads, as compared to AG, AG+HA or AG+FGN microbeads. Importantly, composite microbeads resulted in more even and widespread endothelial network formation, relative to control microbeads consisting of pure fibrin. These results demonstrate that AG+HA+FGN microbeads support HUVEC sprouting both within and between adjacent microbeads, and can promote distributed vascularization of an external matrix. Such modular microtissues may have utility in treating ischemic tissue by rapidly re-establishing a microvascular network. Critical limb ischemia (CLI) is a chronic disease that can lead to tissue necrosis, amputation, and death. Cell-based therapies are being explored to restore blood flow and prevent the complications of CLI. In this study, we developed small, non-aggregating agarose-hydroxyapatite-fibrinogen microbeads that contained endothelial cells and fibroblasts. Microbeads were easy to handle and culture, and endothelial sprouts formed within and between microbeads. Our data demonstrates that the composition of the microbead matrix altered the degree of endothelial sprouting, and that the addition of hydroxyapatite and fibrinogen resulted in more distributed sprouting compared to pure fibrin microbeads. The microbead format and control of the matrix formulation may therefore be useful in developing revascularization strategies for the treatment of ischemic disease. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications.

PubMed

Vedadghavami, Armin; Minooei, Farnaz; Mohammadi, Mohammad Hossein; Khetani, Sultan; Rezaei Kolahchi, Ahmad; Mashayekhan, Shohreh; Sanati-Nezhad, Amir

2017-10-15

Hydrogels have been recognized as crucial biomaterials in the field of tissue engineering, regenerative medicine, and drug delivery applications due to their specific characteristics. These biomaterials benefit from retaining a large amount of water, effective mass transfer, similarity to natural tissues and the ability to form different shapes. However, having relatively poor mechanical properties is a limiting factor associated with hydrogel biomaterials. Controlling the biomechanical properties of hydrogels is of paramount importance. In this work, firstly, mechanical characteristics of hydrogels and methods employed for characterizing these properties are explored. Subsequently, the most common approaches used for tuning mechanical properties of hydrogels including but are not limited to, interpenetrating polymer networks, nanocomposites, self-assembly techniques, and co-polymerization are discussed. The performance of different techniques used for tuning biomechanical properties of hydrogels is further compared. Such techniques involve lithography techniques for replication of tissues with complex mechanical profiles; microfluidic techniques applicable for generating gradients of mechanical properties in hydrogel biomaterials for engineering complex human tissues like intervertebral discs, osteochondral tissues, blood vessels and skin layers; and electrospinning techniques for synthesis of hybrid hydrogels and highly ordered fibers with tunable mechanical and biological properties. We finally discuss future perspectives and challenges for controlling biomimetic hydrogel materials possessing proper biomechanical properties. Hydrogels biomaterials are essential constituting components of engineered tissues with the applications in regenerative medicine and drug delivery. The mechanical properties of hydrogels play crucial roles in regulating the interactions between cells and extracellular matrix and directing the cells phenotype and genotype. Despite significant advances in developing methods and techniques with the ability of tuning the biomechanical properties of hydrogels, there are still challenges regarding the synthesis of hydrogels with complex mechanical profiles as well as limitations in vascularization and patterning of complex structures of natural tissues which barricade the production of sophisticated organs. Therefore, in addition to a review on advanced methods and techniques for measuring a variety of different biomechanical characteristics of hydrogels, the new techniques for enhancing the biomechanics of hydrogels are presented. It is expected that this review will profit future works for regulating the biomechanical properties of hydrogel biomaterials to satisfy the demands of a variety of different human tissues. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Sustained release of adipose-derived stem cells by thermosensitive chitosan/gelatin hydrogel for therapeutic angiogenesis.

PubMed

Cheng, Nai-Chen; Lin, Wei-Jhih; Ling, Thai-Yen; Young, Tai-Horng

2017-03-15

Adipose-derived stem cells (ASCs) secrete several angiogenic growth factors and can be applied to treat ischemic tissue. However, transplantation of dissociated ASCs has frequently resulted in rapid cell death. Therefore, we aimed to develop a thermosensitive chitosan/gelatin hydrogel that is capable of ASC sustained release for therapeutic angiogenesis. By blending gelatin in the chitosan thermosensitive hydrogel, we significantly enhanced the viability of the encapsulated ASCs. During in vitro culturing, the gradual degradation of gelatin led to sustained release of ASCs from the chitosan/gelatin hydrogel. In vitro wound healing assays revealed significantly faster cell migration by co-culturing fibroblasts with ASCs encapsulated in chitosan/gelatin hydrogel compared to pure chitosan hydrogels. Additionally, significantly higher concentrations of vascular endothelial growth factor were found in the supernatant of ASC-encapsulated chitosan/gelatin hydrogels. Co-culturing SVEC4-10 endothelial cells with ASC-encapsulated chitosan/gelatin hydrogels resulted in significantly more tube-like structures, indicating the hydrogel's potential in promoting angiogenesis. Chick embryo chorioallantoic membrane assay and mice wound healing model showed significantly higher capillary density after applying ASC-encapsulated chitosan/gelatin hydrogel. Relative to ASC alone or ASC-encapsulated chitosan hydrogel, more ASCs were also found in the wound tissue on post-wounding day 5 after applying ASC-encapsulated chitosan/gelatin hydrogel. Therefore, chitosan/gelatin thermosensitive hydrogels not only maintain ASC survival, they also enable sustained release of ASCs for therapeutic angiogenesis applications, thereby exhibiting great clinical potential in treating ischemic diseases. Adipose-derived stem cells (ASCs) exhibit great potential to treat ischemic diseases. However, poor delivery methods lead to low cellular survival or dispersal of cells from target sites. In this study, we developed a thermosensitive chitosan/gelatin hydrogel that not only enhances the viability of the encapsulated ASCs, the gradual degradation of gelatin also result in a more porous architecture, leading to sustained release of ASCs from the hydrogel. ASC-encapsulated hydrogel enhanced in vitro wound healing of fibroblasts and tube formation of endothelial cells. It also promoted in vivo angiogenesis in a chick embryo chorioallantoic membrane assay and a mice wound model. Therefore, chitosan/gelatin hydrogel represents an effective delivery system that allows for controlled release of viable ASCs for therapeutic angiogenesis. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bio-inspired self-healing structural color hydrogel

PubMed Central

Fu, Fanfan; Chen, Zhuoyue; Zhao, Ze; Wang, Huan; Shang, Luoran; Gu, Zhongze

2017-01-01

Biologically inspired self-healing structural color hydrogels were developed by adding a glucose oxidase (GOX)- and catalase (CAT)-filled glutaraldehyde cross-linked BSA hydrogel into methacrylated gelatin (GelMA) inverse opal scaffolds. The composite hydrogel materials with the polymerized GelMA scaffold could maintain the stability of an inverse opal structure and its resultant structural colors, whereas the protein hydrogel filler could impart self-healing capability through the reversible covalent attachment of glutaraldehyde to lysine residues of BSA and enzyme additives. A series of unprecedented structural color materials could be created by assembling and healing the elements of the composite hydrogel. In addition, as both the GelMA and the protein hydrogels were derived from organisms, the composite materials presented high biocompatibility and plasticity. These features of self-healing structural color hydrogels make them excellent functional materials for different applications. PMID:28533368

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

PubMed Central

Ding, Xiaochu; Wang, Yadong

2017-01-01

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

Encoding Hydrogel Mechanics via Network Cross-Linking Structure.

PubMed

Schweller, Ryan M; West, Jennifer L

2015-05-11

The effects of mechanical cues on cell behaviors in 3D remain difficult to characterize as the ability to tune hydrogel mechanics often requires changes in the polymer density, potentially altering the material's biochemical and physical characteristics. Additionally, with most PEG diacrylate (PEGDA) hydrogels, forming materials with compressive moduli less than ∼10 kPa has been virtually impossible. Here, we present a new method of controlling the mechanical properties of PEGDA hydrogels independent of polymer chain density through the incorporation of additional vinyl group moieties that interfere with the cross-linking of the network. This modification can tune hydrogel mechanics in a concentration dependent manner from <1 to 17 kPa, a more physiologically relevant range than previously possible with PEG-based hydrogels, without altering the hydrogel's degradation and permeability. Across this range of mechanical properties, endothelial cells (ECs) encapsulated within MMP-2/MMP-9 degradable hydrogels with RGDS adhesive peptides revealed increased cell spreading as hydrogel stiffness decreased in contrast to behavior typically observed for cells on 2D surfaces. EC-pericyte cocultures exhibited vessel-like networks within 3 days in highly compliant hydrogels as compared to a week in stiffer hydrogels. These vessel networks persisted for at least 4 weeks and deposited laminin and collagen IV perivascularly. These results indicate that EC morphogenesis can be regulated using mechanical cues in 3D. Furthermore, controlling hydrogel compliance independent of density allows for the attainment of highly compliant mechanical regimes in materials that can act as customizable cell microenvironments.

Functional nucleic acid-based hydrogels for bioanalytical and biomedical applications

PubMed Central

Mo, Liuting; Lu, Chun-Hua; Fu, Ting

2016-01-01

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

Directing the osteoblastic and chondrocytic differentiations of mesenchymal stem cells: matrix vs. induction media

PubMed Central

He, Jing; Guo, Jianglong; Jiang, Bo; Yao, Ruijuan; Wu, Yao

2017-01-01

Abstract While both induction culture media and matrix have been reported to regulate the stem cell fate, little is known about which factor plays a more decisive role in directing the MSC differentiation lineage as well as the underlying mechanisms. To this aim, we seeded MSCs on HA-collagen and HA-synthetic hydrogel matrixes, which had demonstrated highly different potentials toward osteoblastic and chondrocytic differentiation lineages, respectively, and cultured them with osteogenic, chondrogenic and normal culture media, respectively. A systematic comparison has been carried out on the effects of induction media and matrix on MSC adhesion, cytoskeleton organization, proliferation, and in particular differentiation into the osteoblastic and chondrocytic lineages. The results demonstrated that the matrix selection had a much more profound effect on directing the differentiation lineage than the induction media did. The strong modulation effect on the transcription activities might be the critical factor contributing to the above observations in our study, where canonical Wnt-β-Catenin signal pathway was directly involved in the matrix-driven osteoblastic differentiation. Such findings not only provide a critical insight on natural cellular events leading to the osteoblastic and chondrocytic differentiations, but also have important implications in biomaterial design for tissue engineering applications. PMID:29026640

Influence of dialkyne structure on the properties of new click-gels based on hyaluronic acid.

PubMed

Testa, Gabriella; Di Meo, Chiara; Nardecchia, Stefania; Capitani, Donatella; Mannina, Luisa; Lamanna, Raffaele; Barbetta, Andrea; Dentini, Mariella

2009-08-13

Hydrogels have been widely used in tissue engineering as a support for tissue formation and/or to deliver drug locally. A novel procedure for the in situ rapid chemical gelation of aqueous solutions of hyaluronan (HA) was employed. HA was functionalised with an arm bearing a terminal azido group (HAAA). When HAAA was mixed with a series of dialkyne reagents of different length, a 1,3-dipolar cycloaddition ("click-chemistry") reaction took place in the presence of catalytic amount of Cu(I) resulting in fast gelation at room temperature. The resulting gels were characterised in terms of degree of cross-linking by (1)H HR-MAS NMR. The kinetic of gelation and the determination of elastic moduli as well as the degree of swelling and the controlled release of a model drug, were studied as a function of chemical nature of the dialkyne group, catalyst concentration, HAAA concentration and temperature. All these variables allowed the swelling ratio and the extent of release of a drug, doxorubicin, entrapped within the gel, to be modulated. In all cases the kinetic of release reached the stationary state within 150 h. The height of the plateau was dependent on the overall (chemical and topological) degree of cross-linking.

Chitosan based hydrogels: characteristics and pharmaceutical applications

PubMed Central

Ahmadi, F.; Oveisi, Z.; Samani, S. Mohammadi; Amoozgar, Z.

2015-01-01

Hydrogel scaffolds serve as semi synthetic or synthetic extra cellular matrix to provide an amenable environment for cellular adherence and cellular remodeling in three dimensional structures mimicking that of natural cellular environment. Additionally, hydrogels have the capacity to carry small molecule drugs and/or proteins, growth factors and other necessary components for cell growth and differentiation. In the context of drug delivery, hydrogels can be utilized to localize drugs, increase drugs concentration at the site of action and consequently reduce off-targeted side effects. The current review aims to describe and classify hydrogels and their methods of production. The main highlight is chitosan-based hydrogels as biocompatible and medically relevant hydrogels for drug delivery. PMID:26430453

Development of a self-cleaning sensor membrane for implantable biosensors.

PubMed

Gant, Rebecca M; Hou, Yaping; Grunlan, Melissa A; Coté, Gerard L

2009-09-01

Fibrous tissue encapsulation may slow the diffusion of the target analyte to an implanted sensor and compromise the optical signal. Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels are thermoresponsive, exhibiting temperature-modulated swelling behavior that could be used to prevent biofouling. Unfortunately, PNIPAAm hydrogels are limited by poor mechanical strength. In this study, a unique thermoresponsive nanocomposite hydrogel was developed to create a mechanically robust self-cleaning sensor membrane for implantable biosensors. This hydrogel was prepared by the photochemical cure of an aqueous solution of NIPAAm and copoly(dimethylsiloxane/methylvinylsiloxane) colloidal nanoparticles ( approximately 219 nm). At temperatures above the volume phase transition temperature (VPTT) of approximately 33-34 degrees C, the hydrogel deswells and becomes hydrophobic, whereas lowering the temperature below the VPTT causes the hydrogel to swell and become hydrophilic. The potential of this material to minimize biofouling via temperature-modulation while maintaining sensor viability was investigated using glucose as a target analyte. PNIPAAm composite hydrogels with and without poration were compared to a pure PNIPAAm hydrogel and a nonthermoresponsive poly(ethylene glycol) (PEG) hydrogel. Poration led to a substantial increase in diffusion. Cycling the temperature of the nanocomposite hydrogels around the VPTT caused significant detachment of GFP-H2B 3T3 fibroblast cells.

A robust, highly stretchable supramolecular polymer conductive hydrogel with self-healability and thermo-processability

PubMed Central

Wu, Qian; Wei, Junjie; Xu, Bing; Liu, Xinhua; Wang, Hongbo; Wang, Wei; Wang, Qigang; Liu, Wenguang

2017-01-01

Dual amide hydrogen bond crosslinked and strengthened high strength supramolecular polymer conductive hydrogels were fabricated by simply in situ doping poly (N-acryloyl glycinamide-co-2-acrylamide-2-methylpropanesulfonic) (PNAGA-PAMPS) hydrogels with PEDOT/PSS. The nonswellable conductive hydrogels in PBS demonstrated high mechanical performances—0.22–0.58 MPa tensile strength, 1.02–7.62 MPa compressive strength, and 817–1709% breaking strain. The doping of PEDOT/PSS could significantly improve the specific conductivities of the hydrogels. Cyclic heating and cooling could lead to reversible sol-gel transition and self-healability due to the dynamic breakup and reconstruction of hydrogen bonds. The mending hydrogels recovered not only the mechanical properties, but also conductivities very well. These supramolecular conductive hydrogels could be designed into arbitrary shapes with 3D printing technique, and further, printable electrode can be obtained by blending activated charcoal powder with PNAGA-PAMPS/PEDOT/PSS hydrogel under melting state. The fabricated supercapacitor via the conducting hydrogel electrodes possessed high capacitive performances. These cytocompatible conductive hydrogels have a great potential to be used as electro-active and electrical biomaterials. PMID:28134283

Water-soluble, neutral 3,5-diformyl-BODIPY with extended fluorescence lifetime in a self-healable chitosan hydrogel.

PubMed

Belali, Simin; Emandi, Ganapathi; Cafolla, Atillio A; O'Connell, Barry; Haffner, Benjamin; Möbius, Matthias E; Karimi, Alireza; Senge, Mathias O

2017-11-08

3,5-Diformyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (3,5-diformyl-BODIPY) can be used as an efficient biofunctional cross-linker to generate a new class of chitosan-based hydrogels with fluorescence resonance energy transfer (FRET) dynamics and good solubility in water. The hydrogel was fully characterized by FT-IR, UV-vis, fluorescence, FE-SEM, AFM, rheology and picosecond time-resolved spectroscopic techniques. The self-healing ability was demonstrated by rheological recovery and macroscopic and microscopic observations. The fluorescence lifetime was found to increase in aqueous solution of the BODIPY-chitosan hydrogel compared to the 3,5-diformyl-BODIPY monomer. Calculations based on experimental results such as red-shift and decreased intensity of the emission spectrum of highly dye-concentrated hydrogel in comparison to dilute hydrogels, together with changes in the fluorescence lifetime of the hydrogel at different concentration of dyes, suggest that the BDP-CS hydrogels fluorescence dynamics obey the Förster resonance energy transfer (FRET). Improvements in mechanical and photochemical properties and the acceptable values of BODIPY fluorescence lifetime in the hydrogel matrix indicate the utility of the newly synthesized hydrogels for biomedical applications.

Controlling Mechanical Properties of Cell-Laden Hydrogels by Covalent Incorporation of Graphene Oxide

PubMed Central

Cha, Chaenyung; Shin, Su Ryon; Gao, Xiguang; Annabi, Nasim; Dokmeci, Mehmet R.; Tang, Xiaowu (Shirley); Khademhosseini, Ali

2013-01-01

Graphene-based materials are useful reinforcing agents to modify the mechanical properties of hydrogels. Here, we present an approach to covalently incorporate graphene oxide (GO) into hydrogels via radical copolymerization to enhance the dispersion and conjugation of GO sheets within the hydrogels. GO is chemically modified to present surface-grafted methacrylate groups (MeGO). In comparison to GO, higher concentrations of MeGO can be stably dispersed in a pre-gel solution containing methacrylated gelatin (GelMA) without aggregation or significant increase in viscosity. In addition, the resulting MeGO-GelMA hydrogels demonstrate a significant increase in fracture strength with increasing MeGO concentration. Interestingly, the rigidity of the hydrogels is not significantly affected by the covalently incorporated GO. Therefore, our approach can be used to enhance the structural integrity and resistance to fracture of the hydrogels without inadvertently affecting their rigidity, which is known to affect the behavior of encapsulated cells. The biocompatibility of MeGO-GelMA hydrogels is confirmed by measuring the viability and proliferation of the encapsulated fibroblasts. Overall, this study highlights the advantage of covalently incorporating GO into a hydrogel system, and improves the quality of cell-laden hydrogels. PMID:24127350

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

PubMed

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

2017-02-01

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

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

NASA Astrophysics Data System (ADS)

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

2004-09-01

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

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

PubMed

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

2015-06-01

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

Supramolecular Hydrogels Based on DNA Self-Assembly.

PubMed

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

2017-04-18

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

Programmable DNA Hydrogels Assembled from Multidomain DNA Strands.

PubMed

Jiang, Huiling; Pan, Victor; Vivek, Skanda; Weeks, Eric R; Ke, Yonggang

2016-06-16

Hydrogels are important in biological and medical applications, such as drug delivery and tissue engineering. DNA hydrogels have attracted significant attention due to the programmability and biocompatibility of the material. We developed a series of low-cost one-strand DNA hydrogels self-assembled from single-stranded DNA monomers containing multiple palindromic domains. This new hydrogel design is simple and programmable. Thermal stability, mechanical properties, and loading capacity of these one-strand DNA hydrogels can be readily regulated by simply adjusting the DNA domains. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Poly(ethylene glycol) hydrogel microstructures encapsulating living cells

NASA Technical Reports Server (NTRS)

Koh, Won-Gun; Revzin, Alexander; Pishko, Michael V.

2002-01-01

We present an easy and effective method for the encapsulation of cells inside PEG-based hydrogel microstructures fabricated using photolithography. High-density arrays of three-dimensional microstructures were created on substrates using this method. Mammalian cells were encapsulated in cylindrical hydrogel microstructures of 600 and 50 micrometers in diameter or in cubic hydrogel structures in microfluidic channels. Reducing lateral dimension of the individual hydrogel microstructure to 50 micrometers allowed us to isolate 1-3 cells per microstructure. Viability assays demonstrated that cells remained viable inside these hydrogels after encapsulation for up to 7 days.

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

PubMed

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

2016-07-01

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

3D-Hydrogel Based Polymeric Nanoreactors for Silver Nano-Antimicrobial Composites Generation

PubMed Central

Soto-Quintero, Albanelly; Romo-Uribe, Ángel; Bermúdez-Morales, Víctor H.; Quijada-Garrido, Isabel

2017-01-01

This study underscores the development of Ag hydrogel nanocomposites, as smart substrates for antibacterial uses, via innovative in situ reactive and reduction pathways. To this end, two different synthetic strategies were used. Firstly thiol-acrylate (PSA) based hydrogels were attained via thiol-ene and radical polymerization of polyethylene glycol (PEG) and polycaprolactone (PCL). As a second approach, polyurethane (PU) based hydrogels were achieved by condensation polymerization from diisocyanates and PCL and PEG diols. In fact, these syntheses rendered active three-dimensional (3D) hydrogel matrices which were used as nanoreactors for in situ reduction of AgNO3 to silver nanoparticles. A redox chemistry of stannous catalyst in PU hydrogel yielded spherical AgNPs formation, even at 4 °C in the absence of external reductant; and an appropriate thiol-functionalized polymeric network promoted spherical AgNPs well dispersed through PSA hydrogel network, after heating up the swollen hydrogel at 103 °C in the presence of citrate-reductant. Optical and swelling behaviors of both series of hydrogel nanocomposites were investigated as key factors involved in their antimicrobial efficacy over time. Lastly, in vitro antibacterial activity of Ag loaded hydrogels exposed to Pseudomona aeruginosa and Escherichia coli strains indicated a noticeable sustained inhibitory effect, especially for Ag–PU hydrogel nanocomposites with bacterial inhibition growth capabilities up to 120 h cultivation. PMID:28763050

Polypyrrole/Alginate Hybrid Hydrogels: Electrically Conductive and Soft Biomaterials for Human Mesenchymal Stem Cell Culture and Potential Neural Tissue Engineering Applications.

PubMed

Yang, Sumi; Jang, LindyK; Kim, Semin; Yang, Jongcheol; Yang, Kisuk; Cho, Seung-Woo; Lee, Jae Young

2016-11-01

Electrically conductive biomaterials that can efficiently deliver electrical signals to cells or improve electrical communication among cells have received considerable attention for potential tissue engineering applications. Conductive hydrogels are desirable particularly for neural applications, as they can provide electrical signals and soft microenvironments that can mimic native nerve tissues. In this study, conductive and soft polypyrrole/alginate (PPy/Alg) hydrogels are developed by chemically polymerizing PPy within ionically cross-linked alginate hydrogel networks. The synthesized hydrogels exhibit a Young's modulus of 20-200 kPa. Electrical conductance of the PPy/Alg hydrogels could be enhanced by more than one order of magnitude compared to that of pristine alginate hydrogels. In vitro studies with human bone marrow-derived mesenchymal stem cells (hMSCs) reveal that cell adhesion and growth are promoted on the PPy/Alg hydrogels. Additionally, the PPy/Alg hydrogels support and greatly enhance the expression of neural differentiation markers (i.e., Tuj1 and MAP2) of hMSCs compared to tissue culture plate controls. Subcutaneous implantation of the hydrogels for eight weeks induces mild inflammatory reactions. These soft and conductive hydrogels will serve as a useful platform to study the effects of electrical and mechanical signals on stem cells and/or neural cells and to develop multifunctional neural tissue engineering scaffolds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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

2018-05-29

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

Programmable Hydrogels for Cell Encapsulation and Neo-Tissue Growth to Enable Personalized Tissue Engineering.

PubMed

Bryant, Stephanie J; Vernerey, Franck J

2018-01-01

Biomimetic and biodegradable synthetic hydrogels are emerging as a promising platform for cell encapsulation and tissue engineering. Notably, synthetic-based hydrogels offer highly programmable macroscopic properties (e.g., mechanical, swelling and transport properties) and degradation profiles through control over several tunable parameters (e.g., the initial network structure, degradation kinetics and behavior, and polymer properties). One component to success is the ability to maintain structural integrity as the hydrogel transitions to neo-tissue. This seamless transition is complicated by the fact that cellular activity is highly variable among donors. Thus, computational models provide an important tool in tissue engineering due to their unique ability to explore the coupled processes of hydrogel degradation and neo-tissue growth across multiple length scales. In addition, such models provide new opportunities to develop predictive computational tools to overcome the challenges with designing hydrogels for different donors. In this report, programmable properties of synthetic-based hydrogels and their relation to the hydrogel's structural properties and their evolution with degradation are reviewed. This is followed by recent progress on the development of computational models that describe hydrogel degradation with neo-tissue growth when cells are encapsulated in a hydrogel. Finally, the potential for predictive models to enable patient-specific hydrogel designs for personalized tissue engineering is discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Injectable self-healing carboxymethyl chitosan-zinc supramolecular hydrogels and their antibacterial activity.

PubMed

Wahid, Fazli; Zhou, Ya-Ning; Wang, Hai-Song; Wan, Tong; Zhong, Cheng; Chu, Li-Qiang

2018-04-07

Injectable and self-healing hydrogels have found numerous applications in drug delivery, tissue engineering and 3D cell culture. Herein, we report an injectable self-healing carboxymethyl chitosan (CMCh) supramolecular hydrogels cross-linked by zinc ions (Zn 2+ ). Supramolecular hydrogels were obtained by simple addition of metal ions solution to CMCh solution at an appropriate pH value. The mechanical properties of these hydrogels were adjustable by the concentration of Zn 2+ . For example, the hydrogel with the highest concentration of Zn 2+ (CMCh-Zn4) showed strongest mechanical properties (storage modulus~11,000Pa) while hydrogel with the lowest concentration of Zn 2+ (CMCh-Zn1) showed weakest mechanical properties (storage modulus~220Pa). As observed visually and confirmed rheologically, the CMCh-Zn1 hydrogel with the lowest Zn 2+ concentration showed thixotropic property. CMCh-Zn1 hydrogel also presented injectable property. Moreover, the antibacterial properties of the prepared supramolecular hydrogels were studied against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) by agar well diffusion method. The results revealed Zn 2+ dependent antibacterial properties against both kinds of strains. The inhibition zones were ranging from ~11-24mm and ~10-22mm against S. aureus and E. coli, respectively. We believe that the prepared supramolecular hydrogels could be used as a potential candidate in biomedical fields. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-02-28

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

Hydraulic hydrogel actuators and robots optically and sonically camouflaged in water

PubMed Central

Yuk, Hyunwoo; Lin, Shaoting; Ma, Chu; Takaffoli, Mahdi; Fang, Nicolas X.; Zhao, Xuanhe

2017-01-01

Sea animals such as leptocephali develop tissues and organs composed of active transparent hydrogels to achieve agile motions and natural camouflage in water. Hydrogel-based actuators that can imitate the capabilities of leptocephali will enable new applications in diverse fields. However, existing hydrogel actuators, mostly osmotic-driven, are intrinsically low-speed and/or low-force; and their camouflage capabilities have not been explored. Here we show that hydraulic actuations of hydrogels with designed structures and properties can give soft actuators and robots that are high-speed, high-force, and optically and sonically camouflaged in water. The hydrogel actuators and robots can maintain their robustness and functionality over multiple cycles of actuations, owing to the anti-fatigue property of the hydrogel under moderate stresses. We further demonstrate that the agile and transparent hydrogel actuators and robots perform extraordinary functions including swimming, kicking rubber-balls and even catching a live fish in water. PMID:28145412

Fabrication of patterned calcium cross-linked alginate hydrogel films and coatings through reductive cation exchange.

PubMed

Bruchet, Marion; Melman, Artem

2015-10-20

Calcium cross-linked alginate hydrogels are widely used in targeted drug delivery, tissue engineering, wound treatment, and other biomedical applications. We developed a method for preparing homogeneous alginate hydrogels cross-linked with Ca(2+) cations using reductive cation exchange in homogeneous iron(III) cross-linked alginate hydrogels. Treatment of iron(III) cross-linked alginate hydrogels with calcium salts and sodium ascorbate results in reduction of iron(III) cations to iron(II) that are instantaneously replaced with Ca(2+) cations, producing homogeneous ionically cross-linking hydrogels. Alternatively, the cation exchange can be performed by photochemical reduction in the presence of calcium chloride using a sacrificial photoreductant. This approach allows fabrication of patterned calcium alginate hydrogels through photochemical patterning of iron(III) cross-linked alginate hydrogel followed by the photochemical reductive exchange of iron cations to calcium. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hydrogel scaffolds for tissue engineering: Progress and challenges

PubMed Central

El-Sherbiny, Ibrahim M.; Yacoub, Magdi H.

2013-01-01

Designing of biologically active scaffolds with optimal characteristics is one of the key factors for successful tissue engineering. Recently, hydrogels have received a considerable interest as leading candidates for engineered tissue scaffolds due to their unique compositional and structural similarities to the natural extracellular matrix, in addition to their desirable framework for cellular proliferation and survival. More recently, the ability to control the shape, porosity, surface morphology, and size of hydrogel scaffolds has created new opportunities to overcome various challenges in tissue engineering such as vascularization, tissue architecture and simultaneous seeding of multiple cells. This review provides an overview of the different types of hydrogels, the approaches that can be used to fabricate hydrogel matrices with specific features and the recent applications of hydrogels in tissue engineering. Special attention was given to the various design considerations for an efficient hydrogel scaffold in tissue engineering. Also, the challenges associated with the use of hydrogel scaffolds were described. PMID:24689032

Composites of Polymer Hydrogels and Nanoparticulate Systems for Biomedical and Pharmaceutical Applications

PubMed Central

Zhao, Fuli; Yao, Dan; Guo, Ruiwei; Deng, Liandong; Dong, Anjie; Zhang, Jianhua

2015-01-01

Due to their unique structures and properties, three-dimensional hydrogels and nanostructured particles have been widely studied and shown a very high potential for medical, therapeutic and diagnostic applications. However, hydrogels and nanoparticulate systems have respective disadvantages that limit their widespread applications. Recently, the incorporation of nanostructured fillers into hydrogels has been developed as an innovative means for the creation of novel materials with diverse functionality in order to meet new challenges. In this review, the fundamentals of hydrogels and nanoparticles (NPs) were briefly discussed, and then we comprehensively summarized recent advances in the design, synthesis, functionalization and application of nanocomposite hydrogels with enhanced mechanical, biological and physicochemical properties. Moreover, the current challenges and future opportunities for the use of these promising materials in the biomedical sector, especially the nanocomposite hydrogels produced from hydrogels and polymeric NPs, are discussed. PMID:28347111

Effect of silane coupling agents on the chemical and physical properties of photocrosslinked poly(dimethylsiloxane) dimethacrylate/poly(ethylene glycol) diacrylate hydrogel

NASA Astrophysics Data System (ADS)

Lim, K. W.; Hamid, Z. A. A.

2017-07-01

Inorganic-organic hydrogels based on dimethacrylated polydimethylsiloxane (PDMSMA) and diacrylated poly(ethylene glycol) (PEGDA) macromers were prepared via photocrosslinking method. Silane coupling agent was incorporated into the hydrogel formulations to overcome the phase incompatibility. Pure PEGDA (0:100) hydrogels showed the highest value of ESR %, while pure PDMSMA (100:0) hydrogels showed no swelling as we expected. Inclusion of more hydrophobic domains resulted in a lower value of ESR %, i.e. in 75:25 hybrid hydrogels. Beside, we had noticed 50:50 and 75:25 hybrid hydrogels disintegrate during swelling period. However, their integrity was improved and sustained after the coupling agent was added. Similarly, the value of E* for the hybrid hydrogels showed an increment after the coupling agent was incorporated, and this is in a good agreement with the SEM micrograph which display an improved interfacial adhesion.

An in situ formed biodegradable hydrogel for reconstruction of the corneal endothelium.

PubMed

Liang, Ye; Liu, Wanshun; Han, Baoqin; Yang, Chaozhong; Ma, Qun; Song, Fulai; Bi, Qingqing

2011-01-01

Biodegradable hydrogels are important biomaterials for tissue engineering and drug delivery. For the purpose of corneal regenerative medicine, we describe an in situ formed hydrogel based on a water-soluble derivative of chitosan, hydroxypropyl chitosan (HPCTS), and sodium alginate dialdehyde (SAD). Periodate oxidized alginate rapidly cross-links HPCTS due to Schiff's base formation between the available aldehyde and amino groups. Hydrogel cytotoxicity, degradability and histocompatibility in vivo were examined. The potential of the composite hydrogel for corneal endothelium reconstruction was demonstrated by encapsulating corneal endothelial cells (CECs) to grow on Descemet's membranes. The results demonstrate that the composite hydrogel was both non-toxic and biodegradable and that CECs transplanted by the composite hydrogel could survive and retain normal morphology. These results provide an opportunity for corneal endothelium reconstruction based on tissue engineering by the in situ formed composite hydrogel. Copyright © 2010 Elsevier B.V. All rights reserved.

Characterization of superabsorbent hydrogel based on epichlorohydrin crosslink and carboxymethyl functionalization of cassava starch

NASA Astrophysics Data System (ADS)

Muharam, S.; Yuningsih, L. M.; Sumitra, M. R.

2017-07-01

Superabsorbent hydrogel was prepared by epichlorohydrin crosslink of cassava starch. Their swelling improved with added carboxymethyl group on the starch-epichlorohydrin structure. The structure and properties of starch-epichlorohydrin-carboxymethyl hydrogel were measured by SEM, FTIR, water and physiological solution absorption test and water retention test. The result showed that hydrogel displayed macroporous with heterogenous distribution and irregular surface was formed by epichlorohydrin and carboxymethyl bond in the structure of hydrogel. It was confirmed also by the FTIR spectra. The swelling ratio of starch-epichlorohydrin hydrogel to the water is 518 % and increased to 1,028.5 % with carboxymethyl addition on the structure. The best influence of the physiological solution to the swelling ratio of starch-epichlorohydrin-carboxymethyl hydrogel is urea solution. The water retention of starch-epichlorohydrin-carboxymethyl hydrogel in NaCl solution is better than in CaCl2 solution.

Preparation and characterization of poly(vinyl alcohol)/sodium alginate hydrogel with high toughness and electric conductivity.

PubMed

Jiang, Xiancai; Xiang, Nanping; Zhang, Hongxiang; Sun, Yujun; Lin, Zhen; Hou, Linxi

2018-04-15

Development of bio-based hydrogels with good mechanical properties and high electrical conductivity is of great importance for their excellent biocompatibility and biodegradability. Novel electrically conducive and tough poly(vinyl alcohol)/sodium alginate (PVA/SA) composite hydrogel was obtained by a simple method in this paper. PVA and SA were firstly dissolved in distilled water to form the composite solution and the pure PVA/SA hydrogel was obtained through the freezing/thawing process. The pure PVA/SA hydrogels were subsequently immersed into the saturated NaCl aqueous solution to increase the gel strength and conductivity. The effect of the immersing time on the thermal and mechanical properties of PVA/SA hydrogel was studied. The swelling properties and the antiseptic properties of the obtained PVA/SA hydrogel were also studied. This paper provided a novel way for the preparation of tough hydrogel electrolyte. Copyright © 2018. Published by Elsevier Ltd.

Gradient Material Strategies for Hydrogel Optimization in Tissue Engineering Applications

PubMed Central

2018-01-01

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

Hydraulic hydrogel actuators and robots optically and sonically camouflaged in water.

PubMed

Yuk, Hyunwoo; Lin, Shaoting; Ma, Chu; Takaffoli, Mahdi; Fang, Nicolas X; Zhao, Xuanhe

2017-02-01

Sea animals such as leptocephali develop tissues and organs composed of active transparent hydrogels to achieve agile motions and natural camouflage in water. Hydrogel-based actuators that can imitate the capabilities of leptocephali will enable new applications in diverse fields. However, existing hydrogel actuators, mostly osmotic-driven, are intrinsically low-speed and/or low-force; and their camouflage capabilities have not been explored. Here we show that hydraulic actuations of hydrogels with designed structures and properties can give soft actuators and robots that are high-speed, high-force, and optically and sonically camouflaged in water. The hydrogel actuators and robots can maintain their robustness and functionality over multiple cycles of actuations, owing to the anti-fatigue property of the hydrogel under moderate stresses. We further demonstrate that the agile and transparent hydrogel actuators and robots perform extraordinary functions including swimming, kicking rubber-balls and even catching a live fish in water.

Characteristics of Sodium Polyacrylate/Nano-Sized Carbon Hydrogel for Biomedical Patch.

PubMed

Park, Jong-Kyu; Seo, Sun-Kyo; Cho, Seungkwan; Kim, Han-Sung; Lee, Chi-Hwan

2018-03-01

Conductive hydrogels were prepared for biomedical patch in order to improve the electrical conductivity. Sodium polyacrylate and nano-sized carbon were mixed and fabricated by aqueous solution gelation process in various contents of nano-sized carbon with 0.1, 0.5, 1.0 and 2.0 wt%. Sodium polyacrylate/nano-sized carbon conductive hydrogels were investigated by molecular structure, surface morphology and electrical conductivity. The conductivity of the hydrogel/nano-sized carbon conductive hydrogel proved to be 10% higher than conductive hydrogel without nano-sized carbon. However, it was founded that conductive hydrogels with nano-sized carbon content from 0.5 up to 2.0 wt% were remarkably decreased. This may be due to the non-uniform distribution of nano-sized carbon, resulting from agglomerates of nano-sized carbon. The developed hydrogel is intended for use in the medical and cosmetic fields that is applicable to supply micro-current from device to human body.

Hydraulic hydrogel actuators and robots optically and sonically camouflaged in water

NASA Astrophysics Data System (ADS)

Yuk, Hyunwoo; Lin, Shaoting; Ma, Chu; Takaffoli, Mahdi; Fang, Nicolas X.; Zhao, Xuanhe

2017-02-01

Sea animals such as leptocephali develop tissues and organs composed of active transparent hydrogels to achieve agile motions and natural camouflage in water. Hydrogel-based actuators that can imitate the capabilities of leptocephali will enable new applications in diverse fields. However, existing hydrogel actuators, mostly osmotic-driven, are intrinsically low-speed and/or low-force; and their camouflage capabilities have not been explored. Here we show that hydraulic actuations of hydrogels with designed structures and properties can give soft actuators and robots that are high-speed, high-force, and optically and sonically camouflaged in water. The hydrogel actuators and robots can maintain their robustness and functionality over multiple cycles of actuations, owing to the anti-fatigue property of the hydrogel under moderate stresses. We further demonstrate that the agile and transparent hydrogel actuators and robots perform extraordinary functions including swimming, kicking rubber-balls and even catching a live fish in water.

Gel integration for microfluidic applications.

PubMed

Zhang, Xuanqi; Li, Lingjun; Luo, Chunxiong

2016-05-21

Molecular diffusive membranes or materials are important for biological applications in microfluidic systems. Hydrogels are typical materials that offer several advantages, such as free diffusion for small molecules, biocompatibility with most cells, temperature sensitivity, relatively low cost, and ease of production. With the development of microfluidic applications, hydrogels can be integrated into microfluidic systems by soft lithography, flow-solid processes or UV cure methods. Due to their special properties, hydrogels are widely used as fluid control modules, biochemical reaction modules or biological application modules in different applications. Although hydrogels have been used in microfluidic systems for more than ten years, many hydrogels' properties and integrated techniques have not been carefully elaborated. Here, we systematically review the physical properties of hydrogels, general methods for gel-microfluidics integration and applications of this field. Advanced topics and the outlook of hydrogel fabrication and applications are also discussed. We hope this review can help researchers choose suitable methods for their applications using hydrogels.

Tough photoluminescent hydrogels doped with lanthanide.

PubMed

Wang, Mei Xiang; Yang, Can Hui; Liu, Zhen Qi; Zhou, Jinxiong; Xu, Feng; Suo, Zhigang; Yang, Jian Hai; Chen, Yong Mei

2015-03-01

Photoluminescent hydrogels have emerged as novel soft materials with potential applications in many fields. Although many photoluminescent hydrogels have been fabricated, their scope of usage has been severely limited by their poor mechanical performance. Here, a facile strategy is reported for preparing lanthanide (Ln)-alginate/polyacrylamide (PAAm) hydrogels with both high toughness and photoluminescence, which has been achieved by doping Ln(3+) ions (Ln = Eu, Tb, Eu/Tb) into alginate/PAAm hydrogel networks, where Ln(3+) ions serve as both photoluminescent emitters and physical cross-linkers. The resulting hydrogels exhibit versatile advantages including excellent mechanical properties (∼ MPa strength, ≈ 20 tensile strains, ≈ 10(4) kJ m(-3) energy dissipation), good photoluminescent performance, tunable emission color, excellent processability, and cytocompatibility. The developed tough photoluminescent hydrogels hold great promises for expanding the usage scope of hydrogels. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Alginate nanobeads interspersed fibrin network as in situ forming hydrogel for soft tissue engineering.

PubMed

Deepthi, S; Jayakumar, R

2018-06-01

Hydrogels are a class of materials that has the property of injectability and in situ gel formation. This property of hydrogels is manipulated in this study to develop a biomimetic bioresorbable injectable system of alginate nanobeads interspersed in fibrin network. Alginate nanobeads developed by calcium cross-linking yielded a size of 200-500 nm. The alginate nanobeads fibrin hydrogel was formed using dual syringe apparatus. Characterization of the in situ injectable hydrogel was done by SEM, FTIR and Rheometer. The developed hydrogel showed mechanical strength of 19 kPa which provides the suitable compliance for soft tissue engineering. Cytocompatibility studies using human umbilical cord blood derived mesenchymal stem cells showed good attachment, proliferation and infiltration within the hydrogel similar to fibrin gel. The developed in situ forming hydrogel could be a suitable delivery carrier of stem cells for soft tissue regeneration.

Multi-scale Multi-mechanism Design of Tough Hydrogels: Building Dissipation into Stretchy Networks

PubMed Central

Zhao, Xuanhe

2014-01-01

As swollen polymer networks in water, hydrogels are usually brittle. However, hydrogels with high toughness play critical roles in many plant and animal tissues as well as in diverse engineering applications. Here we review the intrinsic mechanisms of a wide variety of tough hydrogels developed over past few decades. We show that tough hydrogels generally possess mechanisms to dissipate substantial mechanical energy but still maintain high elasticity under deformation. The integrations and interactions of different mechanisms for dissipating energy and maintaining elasticity are essential to the design of tough hydrogels. A matrix that combines various mechanisms is constructed for the first time to guide the design of next-generation tough hydrogels. We further highlight that a particularly promising strategy for the design is to implement multiple mechanisms across multiple length scales into nano-, micro-, meso-, and macro-structures of hydrogels. PMID:24834901

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

PubMed

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

2017-09-15

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

Injectable supramolecular hydrogel formed from α-cyclodextrin and PEGylated arginine-functionalized poly(l-lysine) dendron for sustained MMP-9 shRNA plasmid delivery.

PubMed

Lin, Qianming; Yang, Yumeng; Hu, Qian; Guo, Zhong; Liu, Tao; Xu, Jiake; Wu, Jianping; Kirk, Thomas Brett; Ma, Dong; Xue, Wei

2017-02-01

Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-functionalized poly(l-lysine) dendron (PLLD-Arg) by click reaction, and then the synthesized MPEG-PLLD-Arg interacted with α-cyclodextrin (α-CD) to form the supramolecular hydrogel by the host-guest interaction. The gelation dynamics, hydrogel strength and shear viscosity could be modulated by α-CD content in the hydrogel. MPEG-PLLD-Arg was confirmed to bind and deliver gene effectively, and its gene transfection efficiency was significantly higher than PEI-25k under its optimized condition. After gelation, MMP-9 shRNA plasmid (pMMP-9) could be encapsulated into the hydrogel matrix in situ and be released from the hydrogels sustainedly, as the release rate was dependent on α-CD content. The released MPEG-PLLD-Arg/pMMP-9 complex still showed better transfection efficiency than PEI-25k and induced sustained tumor cell apoptosis. Also, in vivo assays indicated that this pMMP-9-loaded supramolecular hydrogel could result in the sustained tumor growth inhibition meanwhile showed good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate for long-term gene therapy. To realize the sustained gene delivery for gene therapy, a supramolecular hydrogel with high-efficiency gene delivery ability was prepared through the host-guest interaction between α-cyclodextrin and PEGylated arginine-functionalized poly(l-lysine) dendron. The obtained hydrogel was injectable and biocompatible with adjustable physicochemical property. More importantly, the hydrogel showed the high-efficiency and sustained gene transfection to our used cells, better than PEI-25k. The supramolecular hydrogel resulted in the sustained tumor growth inhibition meanwhile keep good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate in long-term gene therapy and tissue engineering. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effects of halloysite nanotubes on physical properties and cytocompatibility of alginate composite hydrogels.

PubMed

Huang, Biao; Liu, Mingxian; Long, Zheru; Shen, Yan; Zhou, Changren

2017-01-01

Sodium alginate (SA)/halloysite nanotubes (HNTs) composite hydrogels were successfully prepared by solution blending and cross-linking with calcium ions. HNTs can improve the physical properties and cytocompatibility of composite hydrogels. The static and shear viscosity of SA/HNTs solution increase by the addition of HNTs. FTIR suggests the presence of hydrogen bond interactions between HNTs and SA. The crystal structure of HNTs is retained in the composites as showed by the X-ray diffraction result. A porous structure with pore size of 100-250μm is found in the hydrogels, which can provide a space for cell growth and migration. The compressive mechanical properties of composite hydrogels significantly increase compared to the pure SA hydrogel. The SA/HNTs composite hydrogels with 80% HNTs loading exhibit the compressive stress at 80% strain of 2.99MPa, while the stress at 80% strain of pure SA hydrogel is only 0.8MPa. The dynamic storage modulus of composite hydrogels also markedly increases with HNTs concentration. The differential scanning calorimetry endothermic peak area and swelling ratios in NaCl solution of the composite hydrogels decrease by the addition of HNTs. Preosteoblast (MC3T3-E1) culture results reveal that the SA/HNTs composites especially at relatively low HNTs loading show a significant increase in cells adhesion and proliferation compared to the pure SA hydrogel. All the results demonstrate that the SA/HNTs composite hydrogels show a promising application in bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

Improved Skin Penetration Using In Situ Nanoparticulate Diclofenac Diethylamine in Hydrogel Systems: In Vitro and In Vivo Studies.

PubMed

Sengupta, Soma; Banerjee, Sarita; Sinha, Biswadip; Mukherjee, Biswajit

2016-04-01

Delivering diclofenac diethylamine transdermally by means of a hydrogel is an approach to reduce or avoid systemic toxicity of the drug while providing local action for a prolonged period. In the present investigation, a process was developed to produce nanosize particles (about 10 nm) of diclofenac diethylamine in situ during the development of hydrogel, using simple mixing technique. Hydrogel was developed with polyvinyl alcohol (PVA) (5.8% w/w) and carbopol 71G (1.5% w/w). The formulations were evaluated on the basis of field emission scanning electron microscopy, texture analysis, and the assessment of various physiochemical properties. Viscosity (163-165 cps for hydrogel containing microsize drug particles and 171-173 cps for hydrogel containing nanosize drug particles, respectively) and swelling index (varied between 0.62 and 0.68) data favor the hydrogels for satisfactory topical applications. The measured hardness of the different hydrogels was uniform indicating a uniform spreadability. Data of in vitro skin (cadaver) permeation for 10 h showed that the enhancement ratios of the flux of the formulation containing nanosize drug (without the permeation enhancer) were 9.72 and 1.30 compared to the formulation containing microsized drug and the marketed formulations, respectively. In vivo plasma level of the drug increased predominantly for the hydrogel containing nanosize drug-clusters. The study depicts a simple technique for preparing hydrogel containing nanosize diclofenac diethylamine particles in situ, which can be commercially viable. The study also shows the advantage of the experimental transdermal hydrogel with nanosize drug particles over the hydrogel with microsize drug particles.

Hydrogels with covalent and noncovalent crosslinks

NASA Technical Reports Server (NTRS)

Kilck, Kristi L. (Inventor); Yamaguchi, Nori (Inventor)

2013-01-01

A method for targeted delivery of therapeutic compounds from hydrogels is presented. The method involves administering to a cell a hydrogel in which a therapeutic compound is noncovalently bound to heparin. The hydrogel may contain covalent and non-covalent crosslinks.

Thermosensitive injectable in-situ forming carboxymethyl chitin hydrogel for three-dimensional cell culture.

PubMed

Liu, Hui; Liu, Jia; Qi, Chao; Fang, Yapeng; Zhang, Lina; Zhuo, Renxi; Jiang, Xulin

2016-04-15

Injectable hydrogels have gained great attentions for cell therapy and tissue regeneration as a result of the applications in minimally invasive surgical procedures with the ease of handling and complete filling of the defect area. Here, a novel biodegradable, thermosensitive and injectable carboxymethyl chitin (CMCH) hydrogel was developed for three-dimensional (3D) cell culture. The obtained CMCH solution remained transparent liquid flowing easily at low temperatures and gelled rapidly at 37°C. The gelation time of CMCH hydrogels could be easily tuned by varying temperature and the degree of carboxymethylation, which facilitates the cell encapsulation process at room temperature and in-situ forming hydrogel at body temperature. Moreover, the CMCH-14 hydrogels in PBS buffer remained stable and continuous porous structure and could be degraded in the presence of lysozyme or hyaluronidase. HeLa cells proliferated sustainably and self-assembled to form 3D multicellular spheroids with high cell activity on the surface of CMCH-14 hydrogel. Encapsulation of COS-7 cells within the in-situ forming CMCH hydrogel demonstrated that CMCH hydrogels promoted cell survival and proliferation. In vivo mouse study of the CMCH hydrogels showed good in-situ gel formation and tissue biocompatibility. Thus, the biodegradable thermosensitive injectable CMCH hydrogels hold potential for 3D cell culture and biomedical applications. Biodegradable hydrogels have been widely studied for cell therapy and tissue regeneration. Herein, we report a novel thermosensitive injectable carboxymethyl chitin (CMCH) hydrogel for 3D cell culture, which was synthesized homogeneously from the bioactive natural chitin through the "green" process avoiding using organic solvent. The CMCH solutions exhibited rapid thermoresponsive sol-to-gel phase transition behavior at 37°C with controllable gelation times, which facilitates the cell encapsulation process at room temperature and in-situ forming hydrogel at body temperature. Importantly, in vitro 3D cell culture and in vivo mouse study of the CMCH hydrogel showed promotion of cell survival and proliferation, good in-situ gel formation and biocompatibility. We believe that such thermosensitive injectable CMCH hydrogels would be very useful for biomedical applications, such as tumor model for cancer research, post-operative adhesion prevention, the regeneration of cartilage and central nervous system and so on. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bioadhesive hydrogels for cosmetic applications.

PubMed

Parente, M E; Ochoa Andrade, A; Ares, G; Russo, F; Jiménez-Kairuz, Á

2015-10-01

The use of bioadhesive hydrogels for skin care presents important advantages such as long residence times on the application site and reduced product administration frequency. The aim of the present work was to develop bioadhesive hydrogels for skin application, using caffeine as a model active ingredient. Eight hydrogels were formulated using binary combinations of a primary polymer (carbomer homopolymer type C (Carbopol(®) 980) or kappa carrageenan potassium salt (Gelcarin(®) GP-812 NF)) and a secondary polymer (carbomer copolymer type B (Pemulen(™) TR-1), xanthan gum or guar gum). Hydrogels were characterized by means of physico-chemical (dynamic rheological measurements, spreadability and adhesion measurements) and sensory methods (projective mapping in combination with a check-all-that-apply (CATA) question). Caffeine hydrogels were formulated using two of the most promising formulations regarding adhesion properties and sensory characteristics. In vitro active ingredient release studies were carried out. Hydrogel formulations showed a prevalently elastic rheological behaviour. Complex viscosity of carbomer homopolymer type C hydrogels was higher than that of the kappa carrageenan hydrogels. Besides, complex viscosity values were dependent on the secondary polymer present in the formulation. Significant differences among hydrogels were found in detachment force, work of adhesion and spreading diameter results. Association of projective mapping with CATA allowed to determine similarities and dissimilarities among samples. Cluster analysis associated the samples in two groups. Two hydrogels were selected to study the release of caffeine. Both hydrogels presented similar release profiles which were well described by the Higuchi model. Caffeine release was exclusively controlled by a diffusive process. Physico-chemical and sensory techniques enabled the identification of bioadhesive hydrogel formulations with positive characteristics for cosmetic applications. Formulations which combined carbomer homopolymer type C with xanthan gum or with carbomer copolymer type B were the most promising for bioadhesive skin products. Caffeine release profiles of selected formulations were not statistically different. Both hydrogels gradually released the active ingredient, reaching approximately 80% within the first 5 h, and their profiles were well described by the Higuchi model. In this context, it could be concluded that the selected hydrogels are suitable bioadhesive hydrogel formulations for cosmetic application on the skin. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Exploring natural silk protein sericin for regenerative medicine: an injectable, photoluminescent, cell-adhesive 3D hydrogel.

PubMed

Wang, Zheng; Zhang, Yeshun; Zhang, Jinxiang; Huang, Lei; Liu, Jia; Li, Yongkui; Zhang, Guozheng; Kundu, Subhas C; Wang, Lin

2014-11-20

Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine.

Exploring natural silk protein sericin for regenerative medicine: an injectable, photoluminescent, cell-adhesive 3D hydrogel

PubMed Central

Wang, Zheng; Zhang, Yeshun; Zhang, Jinxiang; Huang, Lei; Liu, Jia; Li, Yongkui; Zhang, Guozheng; Kundu, Subhas C.; Wang, Lin

2014-01-01

Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine. PMID:25412301

Exploring natural silk protein sericin for regenerative medicine: an injectable, photoluminescent, cell-adhesive 3D hydrogel

NASA Astrophysics Data System (ADS)

Wang, Zheng; Zhang, Yeshun; Zhang, Jinxiang; Huang, Lei; Liu, Jia; Li, Yongkui; Zhang, Guozheng; Kundu, Subhas C.; Wang, Lin

2014-11-01

Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine.

Dynamic Coordination of Eu-Iminodiacetate to Control Fluorochromic Response of Polymer Hydrogels to Multistimuli.

PubMed

Weng, Gengsheng; Thanneeru, Srinivas; He, Jie

2018-03-01

New fluorochromic materials that reversibly change their emission properties in response to their environment are of interest for the development of sensors and light-emitting materials. A new design of Eu-containing polymer hydrogels showing fast self-healing and tunable fluorochromic properties in response to five different stimuli, including pH, temperature, metal ions, sonication, and force, is reported. The polymer hydrogels are fabricated using Eu-iminodiacetate (IDA) coordination in a hydrophilic poly(N,N-dimethylacrylamide) matrix. Dynamic metal-ligand coordination allows reversible formation and disruption of hydrogel networks under various stimuli which makes hydrogels self-healable and injectable. Such hydrogels show interesting switchable ON/OFF luminescence along with the sol-gel transition through the reversible formation and dissociation of Eu-IDA complexes upon various stimuli. It is demonstrated that Eu-containing hydrogels display fast and reversible mechanochromic response as well in hydrogels having interpenetrating polymer network. Those multistimuli responsive fluorochromic hydrogels illustrate a new pathway to make smart optical materials, particularly for biological sensors where multistimuli response is required. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Artificial Auricular Cartilage Using Silk Fibroin and Polyvinyl Alcohol Hydrogel

PubMed Central

Lee, Jung Min; Sultan, Md. Tipu; Kim, Soon Hee; Kumar, Vijay; Yeon, Yeung Kyu; Lee, Ok Joo; Park, Chan Hum

2017-01-01

Several methods for auricular cartilage engineering use tissue engineering techniques. However, an ideal method for engineering auricular cartilage has not been reported. To address this issue, we developed a strategy to engineer auricular cartilage using silk fibroin (SF) and polyvinyl alcohol (PVA) hydrogel. We constructed different hydrogels with various ratios of SF and PVA by using salt leaching, silicone mold casting, and freeze-thawing methods. We characterized each of the hydrogels in terms of the swelling ratio, tensile strength, pore size, thermal properties, morphologies, and chemical properties. Based on the cell viability results, we found a blended hydrogel composed of 50% PVA and 50% SF (P50/S50) to be the best hydrogel among the fabricated hydrogels. An intact 3D ear-shaped auricular cartilage formed six weeks after the subcutaneous implantation of a chondrocyte-seeded 3D ear-shaped P50/S50 hydrogel in rats. We observed mature cartilage with a typical lacunar structure both in vitro and in vivo via histological analysis. This study may have potential applications in auricular tissue engineering with a human ear-shaped hydrogel. PMID:28777314

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

PubMed

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

2018-06-01

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

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

PubMed

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

2018-01-01

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

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

PubMed

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

2017-09-01

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

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

PubMed Central

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

2016-01-01

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

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

Development of injectable hydrogels for nucleus pulposus replacement

NASA Astrophysics Data System (ADS)

Thomas, Jonathan D.

Intervertebral disc degeneration has been reported as the underlying cause for 75% of cases of lower back pain and is marked by dehydration of the nucleus pulposus within the intervertebral disc. There have been many implant designs to replace the nucleus pulposus. Some researchers have proposed the replacement of the nucleus pulposus with hydrogel materials. The insertion of devices made from these materials further compromises the annulus of the disc. An ideal nucleus replacement could be injected into the disc space and form a solid in vivo. However, injectable replacements using curing elastomers and thermoplastic materials are not ideal because of the potentially harmful exothermic heat evolved from their reactions and the toxicity of the reactants used. We propose a hydrogel system that can be injected as a liquid at 25°C and solidified to yield a hydrogel within the intervertebral disc at 37°C. In aqueous solutions, these polymers have Lower Critical Solution Temperatures (LCST) between 25-37°C, making them unique candidate materials for this application. Poly(N-isopropylacrylamide) (PNIPAAm) is the most widely studied LCST polymer due to its drastic transition near body temperature. However, by itself, pure PNIPAAm forms a hydrogel that has low water content and can readily undergo plastic deformation. To increase the water content and impart elasticity to PNIPAAm hydrogels, grafted and branched hydrogel systems were created that incorporated the thermogelling PNIPAAm and hydrophilic poly(ethylene glycol) (PEG). In this research, the effects of polymer composition and monomer to initiator ratio, which controls polymer MW, on the in vitro swelling properties (mass, chemical, and compressive mechanical stability) of hydrogels formed from aqueous solutions of these polymers were evaluated. Immersion studies were also conducted in solutions to simulate the osmotic environment of the nucleus pulposus. The effects of repeated compression and unloading cycles on the water content and dimensional recovery of hydrogels made from three candidate polymer formulations were also determined. Unlike PNIPAAm and PEG grafted PNIPAAm hydrogels, PEG branched hydrogels have covalently linked networks. Addition of 7 mol% PEG branches to PNIPAAm resulted in a hydrogel with a higher water content and better elastic recovery than hydrogels made from pure PNIPAAm. PEG branched PNIPAAm hydrogels were shown to have mass, chemical, and compressive mechanical stability in vitro. Furthermore, these hydrogels showed superior dimensional recovery after compressive cycling than pure PNIPAAm and PEG grafted PNIPAAm hydrogels. The 7 mol% PEG branched PNIPAAm hydrogels have suitable swelling and mechanical properties to potentially serve as a nucleus pulposus replacement.

Patient-specific instrumentation for total knee arthroplasty does not match the pre-operative plan as assessed by intra-operative computer-assisted navigation.

PubMed

Scholes, Corey; Sahni, Varun; Lustig, Sebastien; Parker, David A; Coolican, Myles R J

2014-03-01

The introduction of patient-specific instruments (PSI) for guiding bone cuts could increase the incidence of malalignment in primary total knee arthroplasty. The purpose of this study was to assess the agreement between one type of patient-specific instrumentation (Zimmer PSI) and the pre-operative plan with respect to bone cuts and component alignment during TKR using imageless computer navigation. A consecutive series of 30 femoral and tibial guides were assessed in-theatre by the same surgeon using computer navigation. Following surgical exposure, the PSI cutting guides were placed on the joint surface and alignment assessed using the navigation tracker. The difference between in-theatre data and the pre-operative plan was recorded and analysed. The error between in-theatre measurements and pre-operative plan for the femoral and tibial components exceeded 3° for 3 and 17% of the sample, respectively, while the error for total coronal alignment exceeded 3° for 27% of the sample. The present results indicate that alignment with Zimmer PSI cutting blocks, assessed by imageless navigation, does not match the pre-operative plan in a proportion of cases. To prevent unnecessary increases in the incidence of malalignment in primary TKR, it is recommended that these devices should not be used without objective verification of alignment, either in real-time or with post-operative imaging. Further work is required to identify the source of discrepancies and validate these devices prior to routine use. II.

Implant Size Availability Affects Reproduction of Distal Femoral Anatomy.

PubMed

Morris, William Z; Gebhart, Jeremy J; Goldberg, Victor M; Wera, Glenn D

2016-07-01

A total knee arthroplasty system offers more distal femoral implant anterior-posterior (AP) sizes than its predecessor. The purpose of this study is to investigate the impact of increased size availability on an implant system's ability to reproduce the AP dimension of the native distal femur. We measured 200 cadaveric femora with the AP-sizing guides of Zimmer (Warsaw, IN) NexGen (8 sizes) and Zimmer Persona (12 sizes) total knee arthroplasty systems. We defined "size deviation" as the difference in the AP dimension between the anatomic size of the native femur and the closest implant size. We defined satisfactory reproduction of distal femoral dimensions as < 1 mm difference between the implant and native femur size. The NexGen system was associated with a mean 0.46 mm greater implant size deviation than Persona (p < 0.001). When using a 1 mm size deviation as a cutoff for satisfactory replication of the native distal femoral anatomy, 85/200 specimens (42.5%) were a poor fit by NexGen, but a satisfactory fit by Persona. Only 1/200 specimens (0.5%) was a poor fit by Persona, but a satisfactory fit by NexGen (p < 0.001). The novel knee system with 12 versus 8 sizes reproduces the AP dimension of the native distal femur more closely than its predecessor. Further study is needed to determine the clinical impact of these differences. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Polar Perspectives on Art and Science

NASA Astrophysics Data System (ADS)

Rennermalm, A. K.; Salzman, H.; Gustafson, D.

2014-12-01

The rapidly changing climate and environment in polar regions in the 20th and 21st centuries are well documented by scientists. Yet, this understanding is not well disseminated to students and the general public because the language of science is often inaccessible to these groups. To increase participation in science about the changing Polar regions, we organized a series of interdisciplinary events at Rutgers, The State University of New Jersey, in 2013/14 called "Polar Perspectives on Art and Science". This series brought five artist/scholars to Rutgers and reached a broad audience of students, faculty and the general public. Accompanying this series were two high-profile events. First, the Zimmerli Art Museum's academic-year-long exhibit, "Glacial Perspectives," displayed paintings and photographs by Diane Burko documenting rapidly changing glacial, and polar landscapes. Second, the "Let Us Talk About Water" event included a screening of the documentary "Chasing Ice" followed by a panel discussion at the Rutgers Cinema. Financial support was provided by Zimmerli Art Museum's Andrew W. Mellon Endowment Fund, Consortium of Universities for the Advancement of Hydrological Sciences, Inc., Rutgers Centers for Global Advancement and International Affairs, GAIA, and many other Rutgers institutes and departments. Student feedback on the "Polar Perspectives on Science and Art" suggest that art was effective in enhancing engagement and understanding of contemporary polar change. Furthermore, the many events created a forum for reoccurring and stimulating discussions among people with their academic home in widely different disciplines, including humanities, and physical and social sciences.

Fabrication and characterization of graphene hydrogel via hydrothermal approach as a scaffold for preliminary study of cell growth

PubMed Central

Lim, HN; Huang, NM; Lim, SS; Harrison, I; Chia, CH

2011-01-01

Background Three-dimensional assembly of graphene hydrogel is rapidly attracting the interest of researchers because of its wide range of applications in energy storage, electronics, electrochemistry, and waste water treatment. Information on the use of graphene hydrogel for biological purposes is lacking, so we conducted a preliminary study to determine the suitability of graphene hydrogel as a substrate for cell growth, which could potentially be used as building blocks for biomolecules and tissue engineering applications. Methods A three-dimensional structure of graphene hydrogel was prepared via a simple hydrothermal method using two-dimensional large-area graphene oxide nanosheets as a precursor. Results The concentration and lateral size of the graphene oxide nanosheets influenced the structure of the hydrogel. With larger-area graphene oxide nanosheets, the graphene hydrogel could be formed at a lower concentration. X-ray diffraction patterns revealed that the oxide functional groups on the graphene oxide nanosheets were reduced after hydrothermal treatment. The three-dimensional graphene hydrogel matrix was used as a scaffold for proliferation of a MG63 cell line. Conclusion Guided filopodia protrusions of MG63 on the hydrogel were observed on the third day of cell culture, demonstrating compatibility of the graphene hydrogel structure for bioapplications. PMID:21931479

Tough and tunable adhesion of hydrogels: experiments and models

NASA Astrophysics Data System (ADS)

Zhang, Teng; Yuk, Hyunwoo; Lin, Shaoting; Parada, German A.; Zhao, Xuanhe

2017-06-01

As polymer networks infiltrated with water, hydrogels are major constituents of animal and plant bodies and have diverse engineering applications. While natural hydrogels can robustly adhere to other biological materials, such as bonding of tendons and cartilage on bones and adhesive plaques of mussels, it is challenging to achieve such tough adhesions between synthetic hydrogels and engineering materials. Recent experiments show that chemically anchoring long-chain polymer networks of tough synthetic hydrogels on solid surfaces create adhesions tougher than their natural counterparts, but the underlying mechanism has not been well understood. It is also challenging to tune systematically the adhesion of hydrogels on solids. Here, we provide a quantitative understanding of the mechanism for tough adhesions of hydrogels on solid materials via a combination of experiments, theory, and numerical simulations. Using a coupled cohesive-zone and Mullins-effect model validated by experiments, we reveal the interplays of intrinsic work of adhesion, interfacial strength, and energy dissipation in bulk hydrogels in order to achieve tough adhesions. We further show that hydrogel adhesion can be systematically tuned by tailoring the hydrogel geometry and silanization time of solid substrates, corresponding to the control of energy dissipation zone and intrinsic work of adhesion, respectively. The current work further provides a theoretical foundation for rational design of future biocompatible and underwater adhesives.

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

PubMed

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

2018-03-01

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

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

PubMed

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

2018-07-01

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

Influence of Different ECM-Like Hydrogels on Neurite Outgrowth Induced by Adipose Tissue-Derived Stem Cells

PubMed Central

Oliveira, E.; Assunção-Silva, R. C.; Teixeira, F. G.

2017-01-01

Mesenchymal stem cells (MSCs) have been proposed for spinal cord injury (SCI) applications due to their capacity to secrete growth factors and vesicles—secretome—that impacts important phenomena in SCI regeneration. To improve MSC survival into SCI sites, hydrogels have been used as transplantation vehicles. Herein, we hypothesized if different hydrogels could interact differently with adipose tissue-derived MSCs (ASCs). The efficacy of three natural hydrogels, gellan gum (functionalized with a fibronectin peptide), collagen, and a hydrogel rich in laminin epitopes (NVR-gel) in promoting neuritogenesis (alone and cocultured with ASCs), was evaluated in the present study. Their impact on ASC survival, metabolic activity, and gene expression was also evaluated. Our results indicated that all hydrogels supported ASC survival and viability, being this more evident for the functionalized GG hydrogels. Moreover, the presence of different ECM-derived biological cues within the hydrogels appears to differently affect the mRNA levels of growth factors involved in neuronal survival, differentiation, and axonal outgrowth. All the hydrogel-based systems supported axonal growth mediated by ASCs, but this effect was more robust in functionalized GG. The data herein presented highlights the importance of biological cues within hydrogel-based biomaterials as possible modulators of ASC secretome and its effects for SCI applications. PMID:29333166

Structuring and calorie control of bakery products by templating batter with ultra melt-resistant food-grade hydrogel beads.

PubMed

Thompson, Benjamin R; Horozov, Tommy S; Stoyanov, Simeon D; Paunov, Vesselin N

2017-08-01

We report the use of a temperature insensitive, food-grade hydrogel to reduce the caloric density of pancakes that were prepared at temperatures much higher than the boiling point of water. This cheap, facile method utilises a mixed agar-methylcellulose hydrogel, which was blended to produce a slurry of hydrogel microbeads. The pancake batter was mixed with a controlled volume percentage of slurry of hydrogel beads and cooked. From bomb calorimetry experiments, the composites were found to have a reduced caloric density that reflects the volume percentage of hydrogel beads mixed with the batter. Using this procedure, we were able to reduce the caloric density of pancakes by up to 23 ± 3% when the volume percentage of hydrogel beads initially used was 25%. The method is not limited to pancakes and could potentially be applied to various other food products. The structure and morphology of the freeze-dried pancakes and pancake-hydrogel composites were investigated and pores of a similar size to the hydrogel beads were found, confirming that the gel beads maintained their structure during the cooking process. There is scope for further development of this method by the encapsulation of nutritionally beneficial or flavour enhancing ingredients within the hydrogel beads.

Antibacterial Activity of Silver Nanoparticle-Loaded Soft Contact Lens Materials: The Effect of Monomer Composition.

PubMed

Shayani Rad, Maryam; Khameneh, Bahman; Sabeti, Zahra; Mohajeri, Seyed Ahmad; Fazly Bazzaz, Bibi Sedigheh

2016-10-01

In the present work, the effect of monomer composition on silver nanoparticles' (SNPs) binding capacity of hydrogels was investigated and their antibacterial efficacy was evaluated. Three series of poly-hydroxyethyl methacrylate (HEMA) hydrogels were prepared using methacrylic acid (MAA), methacrylamide (MAAM), and 4-vinylpyridine (4VP) as co-monomers, and ethylene glycol dimethacrylate (EGDMA) as cross-linker. SNPs binding capacity of hydrogels was evaluated in different concentrations (2, 10, and 20 ppm). In vitro antibacterial activity of SNP-loaded hydrogels was studied against Pseudomonas aeruginosa (P. aeruginosa) isolated from patients' eyes. Then, inhibitory effect of hydrogels in biofilm formation was evaluated in the presence of Staphylococcus epidermidis (S. epidermidis) (DSMZ 3270). Our data indicated that poly(HEMA-co-MAA-co-EGDMA) had superior binding affinity for SNPs in comparison with other hydrogels. All SNP-loaded hydrogels demonstrated excellent antimicrobial effects at all times against P. aeruginosa and S. epidermidis after soaking in 10 and 20 ppm SNP suspensions. Scanning electron microscope (SEM) images revealed excellent inhibitory effect of SNPs against biofilm formation on the surface of the hydrogels. This study indicated the effect of monomer compositions in SNP loading capacity of poly(HEMA) hydrogels and antibacterial efficacy of SNP-loaded hydrogels against P. aeruginosa and S. epidermidis, but further in vivo evaluation is necessary.

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

PubMed

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

2017-06-05

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

Controlling mechanical properties of cell-laden hydrogels by covalent incorporation of graphene oxide.

PubMed

Cha, Chaenyung; Shin, Su Ryon; Gao, Xiguang; Annabi, Nasim; Dokmeci, Mehmet R; Tang, Xiaowu Shirley; Khademhosseini, Ali

2014-02-12

Graphene-based materials are useful reinforcing agents to modify the mechanical properties of hydrogels. Here, an approach is presented to covalently incorporate graphene oxide (GO) into hydrogels via radical copolymerization to enhance the dispersion and conjugation of GO sheets within the hydrogels. GO is chemically modified to present surface-grafted methacrylate groups (MeGO). In comparison to GO, higher concentrations of MeGO can be stably dispersed in a pre-gel solution containing methacrylated gelatin (GelMA) without aggregation or significant increase in viscosity. In addition, the resulting MeGO-GelMA hydrogels demonstrate a significant increase in fracture strength with increasing MeGO concentration. Interestingly, the rigidity of the hydrogels is not significantly affected by the covalently incorporated GO. Therefore, this approach can be used to enhance the structural integrity and resistance to fracture of the hydrogels without inadvertently affecting their rigidity, which is known to affect the behavior of encapsulated cells. The biocompatibility of MeGO-GelMA hydrogels is confirmed by measuring the viability and proliferation of the encapsulated fibroblasts. Overall, this study highlights the advantage of covalently incorporating GO into a hydrogel system, and improves the quality of cell-laden hydrogels. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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

2016-06-01

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

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

PubMed

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

2016-12-01

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

Methods To Assess Shear-Thinning Hydrogels for Application As Injectable Biomaterials

PubMed Central

2017-01-01

Injectable hydrogels have gained popularity as a vehicle for the delivery of cells, growth factors, and other molecules to localize and improve their retention at the injection site, as well as for the mechanical bulking of tissues. However, there are many factors, such as viscosity, storage and loss moduli, and injection force, to consider when evaluating hydrogels for such applications. There are now numerous tools that can be used to quantitatively assess these factors, including for shear-thinning hydrogels because their properties change under mechanical load. Here, we describe relevant rheological tests and ways to measure injection force using a force sensor or a mechanical testing machine toward the evaluation of injectable hydrogels. Injectable, shear-thinning hydrogels can be used in a variety of clinical applications, and as an example we focus on methods for injection into the heart, where an understanding of injection properties and mechanical forces is imperative for consistent hydrogel delivery and retention. We discuss methods for delivery of hydrogels to mouse, rat, and pig hearts in models of myocardial infarction, and compare methods of tissue postprocessing for hydrogel preservation. Our intent is that the methods described herein can be helpful in the design and assessment of shear-thinning hydrogels for widespread biomedical applications. PMID:29250593

Tumor Growth Suppression Induced by Biomimetic Silk Fibroin Hydrogels

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

Biodegradable HEMA-based hydrogels with enhanced mechanical properties.

PubMed

Moghadam, Mohamadreza Nassajian; Pioletti, Dominique P

2016-08-01

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

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

PubMed

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

2012-01-01

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

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

PubMed

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

2017-07-01

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

PEG-based degradable networks for drug delivery applications

NASA Astrophysics Data System (ADS)

Ostroha, Jamie L.

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

Hydrogel ionotronics

NASA Astrophysics Data System (ADS)

Yang, Canhui; Suo, Zhigang

2018-06-01

An ionotronic device functions by a hybrid circuit of mobile ions and mobile electrons. Hydrogels are stretchable, transparent, ionic conductors that can transmit electrical signals of high frequency over long distance, enabling ionotronic devices such as artificial muscles, skins and axons. Moreover, ionotronic luminescent devices, ionotronic liquid crystal devices, touchpads, triboelectric generators, artificial eels and gel-elastomer-oil devices can be designed based on hydrogels. In this Review, we discuss first-generation hydrogel ionotronic devices and the challenges associated with the mechanical properties and the chemistry of the materials. We examine how strong and stretchable adhesion between hydrophilic and hydrophobic polymer networks can be achieved, how water can be retained in hydrogels and how to design hydrogels that resist fatigue under cyclic loads. Finally, we highlight applications of hydrogel ionotronic devices and discuss the future of the field.

Dextran/Albumin hydrogel sealant for Dacron(R) vascular prosthesis.

PubMed

Lisman, Anna; Butruk, Beata; Wasiak, Iga; Ciach, Tomasz

2014-05-01

In this paper, the authors describe a novel type of hydrogel coating prepared from the copolymer of human serum albumin and oxidized dextran. The material was designed as a hydrogel sealant for polyester (Dacron®)-based vascular grafts. Dextran was chosen as a coating material due to its anti-thrombogenic properties. Prepared hydrogels were compared with similar, already known biomaterial made from gelatine with the same cross-linking agent. Obtained hydrogels, prepared from various ratios of oxidized dextran/albumin or oxidized dextran/gelatine, showed different cross-linking densities, which caused differences in swelling, degradation rate and mechanical properties. Permeability tests confirmed the complete tightness of the hydrogel-modified prosthesis. Results showed that application of the hydrogel coating provided leakage-free prosthesis and eliminated the need of pre-clotting.

New Hydrogels Enriched with Antioxidants from Saffron Crocus Can Find Applications in Wound Treatment and/or Beautification.

PubMed

Zeka, Keti; Ruparelia, Ketan C; Sansone, Claudia; Macchiarelli, Guido; Continenza, Maria Adelaide; Arroo, Randolph R J

2018-01-01

Saffron extracts have a long history of application as skin protectant, possibly due to their ability to scavenge free radicals. In this work, the performance of a hydrogel enriched with antioxidant compounds isolated from saffron crocus (Crocus sativus L.) petals was tested. These hydrogels could be considered as new drug delivery system. Hydrogels are crosslinked polymer networks that absorb large quantities of water but retain the properties of a solid, thus making ideal dressings for sensitive skin. We tested antioxidant-enriched hydrogels on primary mouse fibroblasts. Hydrogels enriched with kaempferol and crocin extracted from saffron petals showed good biocompatibility with in vitro cultured fibroblasts. These new types of hydrogels may find applications in wound treatment and/or beautification. © 2018 S. Karger AG, Basel.

A precision structured smart hydrogel for sensing applications

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

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

A novel injectable temperature-sensitive zinc doped chitosan/β-glycerophosphate hydrogel for bone tissue engineering.

PubMed

Niranjan, Ramesh; Koushik, Chandru; Saravanan, Sekaran; Moorthi, Ambigapathi; Vairamani, Mariappanadar; Selvamurugan, Nagarajan

2013-03-01

Hydrogels are hydrophilic polymers that have a wide range of biomedical applications including bone tissue engineering. In this study we report preparation and characterization of a thermosensitive hydrogel (Zn-CS/β-GP) containing zinc (Zn), chitosan (CS) and beta-glycerophosphate (β-GP) for bone tissue engineering. The prepared hydrogel exhibited a liquid state at room temperature and turned into a gel at body temperature. The hydrogel was characterized by SEM, EDX, XRD, FT-IR and swelling studies. The hydrogel enhanced antibacterial activity and promoted osteoblast differentiation. Thus, we suggest that the Zn-CS/β-GP hydrogel could have potential impact as an injectable in situ forming scaffold for bone tissue engineering applications. Copyright © 2012 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

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

NASA Astrophysics Data System (ADS)

Altunbas, Aysegul

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

Chitosan composite hydrogels reinforced with natural clay nanotubes.

PubMed

Huang, Biao; Liu, Mingxian; Zhou, Changren

2017-11-01

Here, chitosan composites hydrogels were prepared by addition of halloysite nanotubes (HNTs) in the chitosan KOH/LiOH/urea solution. The raw chitosan and chitosan/HNTs composite hydrogels were obtained by heat treatment at 60°C for 8h and then regeneration in ethanol solution. The viscosity of the composite solution is increased with HNTs content. The Fourier transform infrared spectroscopy (FT-IR) shows that the hydrogen bonds interactions exist between the HNTs and the chitosan. X-ray diffraction (XRD) results show that the crystal structure of HNT is not changed in the composite hydrogels. The compressive property test and storage modulus determination show that the mechanical properties and anti-deformation ability of the composite hydrogel significantly increase owing to the reinforcing effect of HNTs. The composites hydrogel with 66.7% HNTs can undergo 7 times compression cycles without breaking with compressive strength of 0.71MPa at 70% deformation, while pure chitosan hydrogel is broken after bearing 5 compression cycles with compressive strength of 0.14MPa and a maximum deformation of 59%. A porous structure with pore size of 100-500μm is found in the composite hydrogels by scanning electron microscopy (SEM), and the pore size and the swelling ratio in NaCl solution decrease by the addition of HNTs and the immersing of ethanol. Chitosan/HNTs composite hydrogels show low cytotoxicity towards MC3T3-E1 cells. Also, the composite hydrogels show a maximum drug entrapment efficiency of 45.7% for doxorubicin (DOX) which is much higher than that of pure chitosan hydrogel (27.5%). All the results illustrate that the chitosan/HNTs composite hydrogels show promising applications as biomaterials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Collagen hydrogels incorporated with surface-aminated mesoporous nanobioactive glass: Improvement of physicochemical stability and mechanical properties is effective for hard tissue engineering.

PubMed

El-Fiqi, Ahmed; Lee, Jae Ho; Lee, Eun-Jung; Kim, Hae-Won

2013-12-01

Collagen (Col) hydrogels have poor physicochemical and mechanical properties and are susceptible to substantial shrinkage during cell culture, which limits their potential applications in hard tissue engineering. Here, we developed novel nanocomposite hydrogels made of collagen and mesoporous bioactive glass nanoparticles (mBGns) with surface amination, and addressed the effects of mBGn addition (Col:mBG = 2:1, 1:1 and 1:2) and its surface amination on the physicochemical and mechanical properties of the hydrogels. The amination of mBGn was shown to enable chemical bonding with collagen molecules. As a result, the nanocomposite hydrogels exhibited a significantly improved physicochemical and mechanical stability. The hydrolytic and enzymatic degradation of the Col-mBGn hydrogels were slowed down due to the incorporation of mBGn and its surface amination. The mechanical properties of the hydrogels, specifically the resistance to loading as well as the stiffness, significantly increased with the addition of mBGn and its aminated form, as assessed by a dynamic mechanical analysis. Mesenchymal stem cells cultivated within the Col-mBGn hydrogels were highly viable, with enhanced cytoskeletal extensions, due to the addition of surface aminated mBGn. While the Col hydrogel showed extensive shrinkage (down to ∼20% of initial size) during a few days of culture, the shrinkage of the mBGn-added hydrogel was substantially reduced, and the aminated mBGn-added hydrogel had no observable shrinkage over 21 days. Results demonstrated the effective roles of aminated mBGn in significantly improving the physicochemical and mechanical properties of Col hydrogel, which are ultimately favorable for applications in stem cell culture for bone tissue engineering. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Gelatin- and starch-based hydrogels. Part B: In vitro mesenchymal stem cell behavior on the hydrogels.

PubMed

Van Nieuwenhove, Ine; Salamon, Achim; Adam, Stefanie; Dubruel, Peter; Van Vlierberghe, Sandra; Peters, Kirsten

2017-04-01

Tissue regeneration often occurs only to a limited extent. By providing a three-dimensional matrix serving as a surrogate extracellular matrix that promotes adult stem cell adhesion, proliferation and differentiation, scaffold-guided tissue regeneration aims at overcoming this limitation. In this study, we applied hydrogels made from crosslinkable gelatin, the hydrolyzed form of collagen, and functionalized starch which were characterized in depth and optimized as described in Van Nieuwenhove et al., 2016. "Gelatin- and Starch-Based Hydrogels. Part A: Hydrogel Development, Characterization and Coating", Carbohydrate Polymers 152:129-39. Collagen is the main structural protein in animal connective tissue and the most abundant protein in mammals. Starch is a carbohydrate consisting of a mixture of amylose and amylopectin. Hydrogels were developed with varying chemical composition (ratio of starch to gelatin applied) and different degrees of methacrylation of the applied gelatin phase. The hydrogels used exhibited no adverse effect on viability of the stem cells cultured on them. Moreover, initial cell adhesion did not differ significantly between them, while the strongest proliferation was observed on the hydrogel with the highest degree of cross-linking. On the least crosslinked and thus most flexible hydrogels, the highest degree of adipogenic differentiation was found, while osteogenic differentiation was the strongest on the most rigid, starch-blended hydrogels. Hydrogel coating with extracellular matrix compounds aggrecan or fibronectin prior to cell seeding exhibited no significant effects. Thus, gelatin-based hydrogels can be optimized regarding maximum promotion of either adipogenic or osteogenic stem cell differentiation in vitro, which makes them promising candidates for in vivo evaluation in clinical studies aiming at either soft or hard tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytotoxicity and metal ions removal using antibacterial biodegradable hydrogels based on N-quaternized chitosan/poly(acrylic acid).

PubMed

Mohamed, Riham R; Elella, Mahmoud H Abu; Sabaa, Magdy W

2017-05-01

Physically crosslinked hydrogels resulted from interaction between N,N,N-trimethyl chitosan chloride (N-Quaternized Chitosan) (NQC) and poly(acrylic acid) (PAA) were synthesized in different weight ratios (3:1), (1:1) and (1:3) taking the following codes Q3P1, Q1P1 and Q1P3, respectively. Characterization of the mentioned hydrogels was done using several analysis tools including; FTIR, XRD, SEM, TGA, biodegradation in simulated body fluid (SBF) and cytotoxicity against HepG-2 liver cancer cells. FTIR results proved that the prepared hydrogels were formed via electrostatic and H-bonding interactions, while XRD patterns proved that the prepared hydrogels -irrespective to their ratios- were more crystalline than both matrices NQC and PAA. TGA results, on the other hand, revealed that Q1P3 hydrogel was the most thermally stable compared to the other two hydrogels (Q3P1 and Q1P1). Biodegradation tests in SBF proved that these hydrogels were more biodegradable than the native chitosan. Examination of the prepared hydrogels for their potency in heavy metal ions removal revealed that they adsorbed Fe (III) and Cd (II) ions more than chitosan, while they adsorbed Cr (III), Ni (II) and Cu (II) ions less than chitosan. Moreover, testing the prepared hydrogels as antibacterial agents towards several Gram positive and Gram negative bacteria revealed their higher antibacterial activity as compared with NQC when used alone. Evaluating the cytotoxic effect of these hydrogels on an in vitro human liver cancer cell model (HepG-2) showed their good cytotoxic activity towards HepG-2. Moreover, the inhibition rate increased with increasing the hydrogels concentration in the culture medium. Copyright © 2017 Elsevier B.V. All rights reserved.

Establishment of a Physical Model for Solute Diffusion in Hydrogel: Understanding the Diffusion of Proteins in Poly(sulfobetaine methacrylate) Hydrogel.

PubMed

Zhou, Yuhang; Li, Junjie; Zhang, Ying; Dong, Dianyu; Zhang, Ershuai; Ji, Feng; Qin, Zhihui; Yang, Jun; Yao, Fanglian

2017-02-02

Prediction of the diffusion coefficient of solute, especially bioactive molecules, in hydrogel is significant in the biomedical field. Considering the randomness of solute movement in a hydrogel network, a physical diffusion RMP-1 model based on obstruction theory was established in this study. The physical properties of the solute and the polymer chain and their interactions were introduced into this model. Furthermore, models RMP-2 and RMP-3 were established to understand and predict the diffusion behaviors of proteins in hydrogel. In addition, zwitterionic poly(sulfobetaine methacrylate) (PSBMA) hydrogels with wide range and fine adjustable mesh sizes were prepared and used as efficient experimental platforms for model validation. The Flory characteristic ratios, Flory-Huggins parameter, mesh size, and polymer chain radii of PSBMA hydrogels were determined. The diffusion coefficients of the proteins (bovine serum albumin, immunoglobulin G, and lysozyme) in PSBMA hydrogels were studied by the fluorescence recovery after photobleaching technique. The measured diffusion coefficients were compared with the predictions of obstruction models, and it was found that our model presented an excellent predictive ability. Furthermore, the assessment of our model revealed that protein diffusion in PSBMA hydrogel would be affected by the physical properties of the protein and the PSBMA network. It was also confirmed that the diffusion behaviors of protein in zwitterionic hydrogels can be adjusted by changing the cross-linking density of the hydrogel and the ionic strength of the swelling medium. Our model is expected to possess accurate predictive ability for the diffusion coefficient of solute in hydrogel, which will be widely used in the biomedical field.

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

On the role of hydrogel structure and degradation in controlling the transport of cell-secreted matrix molecules for engineered cartilage.

PubMed

Dhote, Valentin; Skaalure, Stacey; Akalp, Umut; Roberts, Justine; Bryant, Stephanie J; Vernerey, Franck J

2013-03-01

Damage to cartilage caused by injury or disease can lead to pain and loss of mobility, diminishing one's quality of life. Because cartilage has a limited capacity for self-repair, tissue engineering strategies, such as cells encapsulated in synthetic hydrogels, are being investigated as a means to restore the damaged cartilage. However, strategies to date are suboptimal in part because designing degradable hydrogels is complicated by structural and temporal complexities of the gel and evolving tissue along multiple length scales. To address this problem, this study proposes a multi-scale mechanical model using a triphasic formulation (solid, fluid, unbound matrix molecules) based on a single chondrocyte releasing extracellular matrix molecules within a degrading hydrogel. This model describes the key players (cells, proteoglycans, collagen) of the biological system within the hydrogel encompassing different length scales. Two mechanisms are included: temporal changes of bulk properties due to hydrogel degradation, and matrix transport. Numerical results demonstrate that the temporal change of bulk properties is a decisive factor in the diffusion of unbound matrix molecules through the hydrogel. Transport of matrix molecules in the hydrogel contributes both to the development of the pericellular matrix and the extracellular matrix and is dependent on the relative size of matrix molecules and the hydrogel mesh. The numerical results also demonstrate that osmotic pressure, which leads to changes in mesh size, is a key parameter for achieving a larger diffusivity for matrix molecules in the hydrogel. The numerical model is confirmed with experimental results of matrix synthesis by chondrocytes in biodegradable poly(ethylene glycol)-based hydrogels. This model may ultimately be used to predict key hydrogel design parameters towards achieving optimal cartilage growth. Copyright © 2012 Elsevier Ltd. All rights reserved.

On the role of hydrogel structure and degradation in controlling the transport of cell-secreted matrix molecules for engineered cartilage

PubMed Central

Dhote, Valentin; Skaalure, Stacey; Akalp, Umut; Roberts, Justine; Bryant, Stephanie J.; Vernerey, Franck J.

2012-01-01

Damage to cartilage caused by injury or disease can lead to pain and loss of mobility, diminishing one’s quality of life. Because cartilage has a limited capacity for self-repair, tissue engineering strategies, such as cells encapsulated in synthetic hydrogels, are being investigated as a means to restore the damaged cartilage. However, strategies to date are suboptimal in part because designing degradable hydrogels is complicated by structural and temporal complexities of the gel and evolving tissue along multiple length scales. To address this problem, this study proposes a multi-scale mechanical model using a triphasic formulation (solid, fluid, unbound matrix molecules) based on a single chondrocyte releasing extracellular matrix molecules within a degrading hydrogel. This model describes the key players (cells, proteoglycans, collagen) of the biological system within the hydrogel encompassing different length scales. Two mechanisms are included: temporal changes of bulk properties due to hydrogel degradation, and matrix transport. Numerical results demonstrate that the temporal change of bulk properties is a decisive factor in the diffusion of unbound matrix molecules through the hydrogel. Transport of matrix molecules in the hydrogel contributes both to the development of the pericellular matrix and the extracellular matrix and is dependent on the relative size of matrix molecules and the hydrogel mesh. The numerical results also demonstrate that osmotic pressure, which leads to changes in mesh size, is a key parameter for achieving a larger diffusivity for matrix molecules in the hydrogel. The numerical model is confirmed with experimental results of matrix synthesis by chondrocytes in biodegradable poly(ethylene glycol)-based hydrogels. This model may ultimately be used to predict key hydrogel design parameters towards achieving optimal cartilage growth. PMID:23276516

Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects

PubMed Central

Kim, Sungwoo; Bedigrew, Katherine; Guda, Teja; Maloney, William J.; Park, Sangwon; Wenke, Joseph C.; Yang, Yunzhi Peter

2014-01-01

The purpose of this study was to develop and characterize a novel photo-cross-linkable chitosan-lactide-fibrinogen (CLF) hydrogel and evaluate the efficacy of bone morphogenetic protein-2 (BMP-2) containing CLF hydrogel for osteogenesis in vitro and in vivo. We synthesized the CLF hydrogels and characterized their chemical structure, degradation rate, compressive modulus, and in vitro BMP-2 release kinetics. We evaluated bioactivities of the BMP-2 containing CLF hydrogels (0, 50, 100, and 500 ng/ml) in vitro using W-20-17 preosteoblast mouse bone marrow stromal cells and C2C12 mouse myoblast cells. The effect of BMP-2 containing CLF gels (0, 0.5, 1, 2, and 5μg) on bone formation was evaluated using rat critical size segmental bone defects for 4 weeks. FTIR spectra and SEM images showed chemical and structural changes by addition of fibrinogen into chitosan-lactide copolymer. Incorporation of fibrinogen molecules significantly increased compressive modulus of the hydrogels. In vitro BMP-2 release study showed initial burst releases from the CLF hydrogels followed by sustained releases, regardless of the concentration of the BMP-2 over 4 weeks. Cells in all groups were viable in the presence of the hydrogels regardless of BMP-2 doses, indicating non-cytotoxicity of hydrogels. Alkaline phosphate activity and mineralization of cells exhibited dose dependence on BMP-2 containing CLF hydrogels. Radiographs, microcomputed tomography, and histology confirmed that the BMP-2 containing CLF hydrogels prompted neo-osteogenesis and accelerated healing of the defects in a dose-dependent manner. Thus the CLF hydrogel is a promising delivery system of growth factors for bone regeneration. PMID:25174669

Injectable nanocomposite cryogels for versatile protein drug delivery.

PubMed

Koshy, Sandeep T; Zhang, David K Y; Grolman, Joshua M; Stafford, Alexander G; Mooney, David J

2018-01-01

Sustained, localized protein delivery can enhance the safety and activity of protein drugs in diverse disease settings. While hydrogel systems are widely studied as vehicles for protein delivery, they often suffer from rapid release of encapsulated cargo, leading to a narrow duration of therapy, and protein cargo can be denatured by incompatibility with the hydrogel crosslinking chemistry. In this work, we describe injectable nanocomposite hydrogels that are capable of sustained, bioactive, release of a variety of encapsulated proteins. Injectable and porous cryogels were formed by bio-orthogonal crosslinking of alginate using tetrazine-norbornene coupling. To provide sustained release from these hydrogels, protein cargo was pre-adsorbed to charged Laponite nanoparticles that were incorporated within the walls of the cryogels. The presence of Laponite particles substantially hindered the release of a number of proteins that otherwise showed burst release from these hydrogels. By modifying the Laponite content within the hydrogels, the kinetics of protein release could be precisely tuned. This versatile strategy to control protein release simplifies the design of hydrogel drug delivery systems. Here we present an injectable nanocomposite hydrogel for simple and versatile controlled release of therapeutic proteins. Protein release from hydrogels often requires first entrapping the protein in particles and embedding these particles within the hydrogel to allow controlled protein release. This pre-encapsulation process can be cumbersome, can damage the protein's activity, and must be optimized for each protein of interest. The strategy presented in this work simply premixes the protein with charged nanoparticles that bind strongly with the protein. These protein-laden particles are then placed within a hydrogel and slowly release the protein into the surrounding environment. Using this method, tunable release from an injectable hydrogel can be achieved for a variety of proteins. This strategy greatly simplifies the design of hydrogel systems for therapeutic protein release applications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Therapeutic-Ultrasound-Triggered Shape Memory of a Melamine-Enhanced Poly(vinyl alcohol) Physical Hydrogel.

PubMed

Li, Guo; Yan, Qiang; Xia, Hesheng; Zhao, Yue

2015-06-10

Therapeutic-ultrasound-triggered shape memory was demonstrated for the first time with a melamine-enhanced poly(vinyl alcohol) (PVA) physical hydrogel. The addition of a small amount of melamine (up to 1.5 wt %) in PVA results in a strong hydrogel due to the multiple H-bonding between the two constituents. A temporary shape of the hydrogel can be obtained by deformation of the hydrogel (∼65 wt % water) at room temperature, followed by fixation of the deformation by freezing/thawing the hydrogel under strain, which induces crystallization of PVA. We show that the ultrasound delivered by a commercially available device designed for the patient's pain relief could trigger the shape recovery process as a result of ultrasound-induced local heating in the hydrogel that melts the crystallized PVA cross-linking. This hydrogel is thus interesting for potential applications because it combines many desirable properties, being mechanically strong, biocompatible, and self-healable and displaying the shape memory capability triggered by a physiological stimulus.

Adsorption of Heavy Metals by Graphene Oxide/Cellulose Hydrogel Prepared from NaOH/Urea Aqueous Solution

PubMed Central

Chen, Xiong; Zhou, Sukun; Zhang, Liming; You, Tingting; Xu, Feng

2016-01-01

By taking advantage of cellulose, graphene oxide (GO), and the process for crosslinking using epichlorohydrin (ECH), we propose a simple and novel method to prepare GO/cellulose hydrogel with good potential to adsorb metal ions. GO nanosheets containing carboxyl and hydroxyl groups were introduced into the surface of the cellulose hydrogel with retention of the gel structure and its nanoporous property. Due to the introduction of GO, the GO/cellulose composite hydrogels exhibited good compressive strength. Adsorption capacity of Cu2+ significantly increases with an increase in the GO/cellulose ratio and GO/cellulose hydrogel showed high adsorption rates. The calculated adsorption capacities at equilibrium (qecal) for GO/cellulose hydrogel (GO:cellulose = 20:100 in weight) was up to 94.34 mg·g−1, which was much higher than that of the pristine cellulose hydrogels. Furthermore, GO/cellulose hydrogel exhibited high efficient regeneration and metal ion recovery, and high adsorption capacity for Zn2+, Fe3+, and Pb2+. PMID:28773705

Effects of konjac glucomannan on the structure, properties, and drug release characteristics of agarose hydrogels.

PubMed

Yuan, Yi; Wang, Lin; Mu, Ruo-Jun; Gong, Jingni; Wang, Yuyan; Li, Yuanzhao; Ma, Jiaqi; Pang, Jie; Wu, Chunhua

2018-06-15

Pure agarose (AG) hydrogels have strong rigidity and brittleness, which greatly limit their applications. Therefore, in this study, konjac glucomannan (KGM) was used to improve the properties of AG hydrogels. The effect of KGM on the structure and properties of AG hydrogels was investigated by rotational rheometry, Fourier Transform Infrared Spectroscopy, X-ray Diffraction, and Scanning Electron Microscopy. The results showed that the flexibility of the composite hydrogels increases with KGM concentration, which may be attributed to a synergistic interaction between KGM and AG resulting in a compact network structure. In vitro drug release behavior of composite hydrogels was investigated under different environments using model drug ciprofloxacin. The results showed that the encapsulation, drug loading efficiencies, and sustained release capacity of AG hydrogels were enhanced by the incorporation of KGM. These results suggested that KGM has the potential to enhance the properties and drug release characteristics of AG hydrogels. Copyright © 2018 Elsevier Ltd. All rights reserved.

A novel gelatin hydrogel carrier sheet for corneal endothelial transplantation.

PubMed

Watanabe, Ryou; Hayashi, Ryuhei; Kimura, Yu; Tanaka, Yuji; Kageyama, Tomofumi; Hara, Susumu; Tabata, Yasuhiko; Nishida, Kohji

2011-09-01

We examined the feasibility of using gelatin hydrogels as carrier sheets for the transplantation of cultivated corneal endothelial cells. The mechanical properties, transparency, and permeability of gelatin hydrogel sheets were compared with those of atelocollagen sheets. Immunohistochemistry (ZO-1, Na(+)/K(+)-ATPase, and N-cadherin), hematoxylin and eosin staining, and scanning electron microscopy were performed to assess the integrity of corneal endothelial cells that were cultured on gelatin hydrogel sheets. The gelatin hydrogel sheets displayed greater transparency, elastic modulus, and albumin permeability compared to those of atelocollagen sheets. The corneal endothelial cells on gelatin hydrogel sheets showed normal expression levels of ZO-1, Na(+)/K(+)-ATPase, and N-cadherin. Hematoxylin and eosin staining revealed the formation of a continuous monolayer of cells attached to the gelatin hydrogel sheet. Scanning electron microscopy observations showed that the corneal endothelial cells were arranged in a regular, mosaic, and polygonal pattern with normal cilia. These results indicate that the gelatin hydrogel sheet is a promising material to transport corneal endothelial cells during transplantation.

Gelator-polysaccharide hybrid hydrogel for selective and controllable dye release.

PubMed

Li, Ping; Dou, Xiao-Qiu; Tang, Yi-Tian; Zhu, Shenmin; Gu, Jiajun; Feng, Chuan-Liang; Zhang, Di

2012-12-01

In this paper, 1,4-bi(phenylalanine-diglycol)-benzene (PDB) based Low-Molecular-Weight-Gelator (LMWG) hydrogels are modified using hydrophilic polysaccharide (sodium alginate). A set of techniques including Fourier transform infrared (FT-IR) spectroscopy, (1)H Nuclear Magnetic Resonance ((1)H NMR), X-ray powder diffraction (XRD), Ultraviolet-Visible (UV-Vis), and circular dichroism (CD) had confirmed a β-turn arrangement of PDB gelators and a semi-interpenetrating network (semi-IPN), which was formed through hydrogen bonds between LMWG fibers and polysaccharide chains. The evaluation of physicochemical properties of hydrogels indicates that gelator-polysaccharide hybrid hydrogels possess better mechanical and water retention properties than LMWG hydrogels. The release study of dyes (model drug) from both LMWG and hybrid hydrogels was carried out. Compared with PDB based hydrogels, hybrid hydrogels show a selective and controllable release property for certain dyes. The results suggest LMWG-polysaccharide hybrid gels may find potential applications as promising drug delivery vehicles for drug molecules. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-08-01

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

Polymer Structure and Water States in Salt-Containing Polyampholyte Hydrogels

NASA Astrophysics Data System (ADS)

Li, Xinda; Elliott, Janet A. W.; Lee, Byeongdu; Chung, Hyun-Joong

The phase behavior of water in hydrogels has broad impact on various applications, such as lubrication, adhesion, and electrical conductivity, as well as the hydrogel's low temperature properties. The status of the water molecules is correlated to the structure of the polymer chains in the hydrogel. In this study, the structure and water status of a model charge-balanced polyampholyte poly(4-vinylbenzenesulfonate-co-[3-(methacryloylamino) propyl] trimethylammonium chloride), were investigated by using differential scanning calorimetry (DSC) and small-angle x-ray scattering (SAXS). A globular network structure suggested by SAXS results dictated the depression of the freezing point of water in the hydrogel, as supported by the DSC results. The polyampholyte chains undergo an irreversible collapse during dialysis in deionized water. Such collapsed hydrogels are not able to prevent freezing of water molecules. The results of both synthesis condition and post-synthesis treatments for polyampholyte hydrogels provide us insights to design optimal polyampholyte hydrogels for low temperature applications.

Self-Healing Gelatin Hydrogels Cross-Linked by Combining Multiple Hydrogen Bonding and Ionic Coordination.

PubMed

Zhang, Guangzhao; Lv, Lei; Deng, Yonghong; Wang, Chaoyang

2017-06-01

Self-healing hydrogels have been studied by many researchers via multiple cross-linking approaches including physical and chemical interactions. It is an interesting project in multifunctional hydrogel exploration that a water soluble polymer matrix is cross-linked by combining the ionic coordination and the multiple hydrogen bonds to fabricate self-healing hydrogels with injectable property. This study introduces a general procedure of preparing the hydrogels (termed gelatin-UPy-Fe) cross-linked by both ionic coordination of Fe 3+ and carboxyl group from the gelatin and the quadruple hydrogen bonding interaction from the ureido-pyrimidinone (UPy) dimers. The gelatin-UPy-Fe hydrogels possess an excellent self-healing property. The effects of the ionic coordination of Fe 3+ and quadruple hydrogen bonding of UPy on the formation and mechanical behavior of the prepared hydrogels are investigated. In vitro drug release of the gelatin-UPy-Fe hydrogels is also observed, giving an intriguing glimpse into possible biological applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hydrogel Design for Supporting Neurite Outgrowth and Promoting Gene Delivery to Maximize Neurite Extension

PubMed Central

Shepard, Jaclyn A.; Stevans, Alyson C.; Holland, Samantha; Wang, Christine E.; Shikanov, Ariella; Shea, Lonnie D.

2012-01-01

Hydrogels capable of gene delivery provide a combinatorial approach for nerve regeneration, with the hydrogel supporting neurite outgrowth and gene delivery inducing the expression of inductive factors. This report investigates the design of hydrogels that balance the requirements for supporting neurite growth with those requirements for promoting gene delivery. Enzymatically-degradable PEG hydrogels encapsulating dorsal root ganglia explants, fibroblasts, and lipoplexes encoding nerve growth factor were gelled within channels that can physically guide neurite outgrowth. Transfection of fibroblasts increased with increasing concentration of Arg-Gly-Asp (RGD) cell adhesion sites and decreasing PEG content. The neurite length increased with increasing RGD concentration within 10% PEG hydrogels, yet was maximal within 7.5% PEG hydrogels at intermediate RGD levels. Delivering lipoplexes within the gel produced longer neurites than culture in NGF-supplemented media or co-culture with cells exposed to DNA prior to encapsulation. Hydrogels designed to support neurite outgrowth and deliver gene therapy vectors locally may ultimately be employed to address multiple barriers that limit regeneration. PMID:22038654

Cross-linkable graphene oxide embedded nanocomposite hydrogel with enhanced mechanics and cytocompatibility for tissue engineering.

PubMed

Liu, Xifeng; Miller, A Lee; Waletzki, Brian E; Lu, Lichun

2018-05-01

Graphene oxide (GO) is an attractive material that can be utilized to enhance the modulus and conductivities of substrates and hydrogels. To covalently cross-link graphene oxide sheets into hydrogels, abundant cross-linkable double bonds were introduced to synthesize the graphene-oxide-tris-acrylate sheet (GO-TrisA). Polyacrylamide (PAM) nanocomposite hydrogels were then fabricated with inherent covalently and permanently cross-linked GO-TrisA sheets. Results showed that the covalently cross-linked GO-TrisA/PAM nanocomposite hydrogel had enhanced mechanical strength, thermo stability compared with GO/PAM hydrogel maintained mainly by hydrogen bonding between PAM chains and GO sheets. In vitro cell study showed that the covalently cross-linked rGO-TrisA/PAM nanocomposite hydrogel had excellent cytocompatibility after in situ reduction. These results suggest that rGO-TrisA/PAM nanocomposite hydrogel holds great potential for tissue engineering applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1247-1257, 2018. © 2018 Wiley Periodicals, Inc.

Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds

NASA Astrophysics Data System (ADS)

Seow, Wei Yang; Salgado, Giorgiana; Lane, E. Birgitte; Hauser, Charlotte A. E.

2016-09-01

Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing.

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

PubMed

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

2017-10-01

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

Surface wettability enhancement of silicone hydrogel lenses by processing with polar plastic molds.

PubMed

Lai, Y C; Friends, G D

1997-06-05

In the quest for hydrogel contact lenses with improved extended wear capability, the use of siloxane moieties in the lens materials was investigated. However, the introduction of hydrophobic siloxane groups gave rise to wettability and lipidlike deposit problems. It was found that when polysiloxane-based compositions for hydrogels were processed with polar plastic molds, such as those fabricated from an acrylonitrile-based polymer, the hydrogel lenses fabricated were wettable, with minimized lipidlike deposits. These findings were supported by the wettability of silicone hydrogel films, silicon, and nitrogen element contents near lens surfaces, as well as the results from clinical assessment of silicone hydrogel lenses.

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

PubMed

Iftime, Manuela Maria; Marin, Luminita

2018-07-01

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

Hydrogel research in Germany: the priority programme, Intelligent Hydrogels

NASA Astrophysics Data System (ADS)

Wallmersperger, Thomas; Sadowski, Gabriele

2009-03-01

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

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.

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

PubMed

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

2013-01-01

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

Two-dimensional inverse opal hydrogel for pH sensing.

PubMed

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

2014-12-07

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

Development of swellable local implants of a polyethyleneimine-poly(vinyl pyrrolidone) (PEI-PVP) hydrogel as a socket filler.

PubMed

Chang, Ching-Wen; Ho, Hsiu-O; Lo, Yi-June; Lee, Sheng-Yang; Yang, You-Ren; Sheu, Ming-Thau

2012-01-01

In this study, hydrogels composed of polyethyleneimine (PEI) and poly(vinyl pyrrolidone) K90 (PVP) cross-linked with various concentrations (0, 0.125, 0.25 and 0.5%) of glutaraldehyde were evaluated as a hydrogel filler for the local delivery of lidocaine after tooth extraction. The drug-release kinetics, swellability, cytotoxicity and wound healing after tooth extraction of these non-cross-linked and cross-linked PEI-PVP hydrogels were examined in male beagles and compared to values using Spongostan(®). Results demonstrated that the extent of cross-linking influenced the swelling of the resulting hydrogel, but the drug-release rates were similar. No significant changes were observed in gingival fibroblasts in contact with the PEI- PVP hydrogels or Spongostan(®). In the in vivo study, PEI-PVP hydrogels showed good retention in the socket for 2 days and showed comparable wound-healing rates within 2 weeks with those of Spongostan(®). In conclusion, PEI-PVP hydrogels are suitable for use as socket-dressing materials, and the release of local anaesthesia from PEI-PVP hydrogels can be sustained for a desirable period of time to prevent pain after a tooth extraction.

Material properties that predict preservative uptake for silicone hydrogel contact lenses.

PubMed

Green, J Angelo; Phillips, K Scott; Hitchins, Victoria M; Lucas, Anne D; Shoff, Megan E; Hutter, Joseph C; Rorer, Eva M; Eydelman, Malvina B

2012-11-01

To assess material properties that affect preservative uptake by silicone hydrogel lenses. We evaluated the water content (using differential scanning calorimetry), effective pore size (using probe penetration), and preservative uptake (using high-performance liquid chromatography with spectrophotometric detection) of silicone and conventional hydrogel soft contact lenses. Lenses grouped similarly based on freezable water content as they did based on total water content. Evaluation of the effective pore size highlighted potential differences between the surface-treated and non-surface-treated materials. The water content of the lens materials and ionic charge are associated with the degree of preservative uptake. The current grouping system for testing contact lens-solution interactions separates all silicone hydrogels from conventional hydrogel contact lenses. However, not all silicone hydrogel lenses interact similarly with the same contact lens solution. Based upon the results of our research, we propose that the same material characteristics used to group conventional hydrogel lenses, water content and ionic charge, can also be used to predict uptake of hydrophilic preservatives for silicone hydrogel lenses. In addition, the hydrophobicity of silicone hydrogel contact lenses, although not investigated here, is a unique contact lens material property that should be evaluated for the uptake of relatively hydrophobic preservatives and tear components.

An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering

PubMed Central

Chen, Feng; Yu, Songrui; Liu, Bing; Ni, Yunzhou; Yu, Chunyang; Su, Yue; Zhu, Xinyuan; Yu, Xiaowei; Zhou, Yongfeng; Yan, Deyue

2016-01-01

In this study, an enzymatically cross-linked injectable and biodegradable hydrogel system comprising carboxymethyl pullulan-tyramine (CMP-TA) and chondroitin sulfate-tyramine (CS-TA) conjugates was successfully developed under physiological conditions in the presence of both horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) for cartilage tissue engineering (CTTE). The HRP crosslinking method makes this injectable system feasible, minimally invasive and easily translatable for regenerative medicine applications. The physicochemical properties of the mechanically stable hydrogel system can be modulated by varying the weight ratio and concentration of polymer as well as the concentrations of crosslinking reagents. Additionally, the cellular behaviour of porcine auricular chondrocytes encapsulated into CMP-TA/CS-TA hydrogels demonstrates that the hydrogel system has a good cyto-compatibility. Specifically, compared to the CMP-TA hydrogel, these CMP-TA/CS-TA composite hydrogels have enhanced cell proliferation and increased cartilaginous ECM deposition, which significantly facilitate chondrogenesis. Furthermore, histological analysis indicates that the hydrogel system exhibits acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable pullulan/chondroitin sulfate composite hydrogels presented here are expected to be useful biomaterial scaffold for regenerating cartilage tissue. PMID:26817622

Starch hydrogels: The influence of the amylose content and gelatinization method.

PubMed

Biduski, Bárbara; Silva, Wyller Max Ferreria da; Colussi, Rosana; Halal, Shanise Lisie de Mello El; Lim, Loong-Tak; Dias, Álvaro Renato Guerra; Zavareze, Elessandra da Rosa

2018-07-01

Gelatinization and retrogradation, influenced by amylose and amylopectin ratio, are important characteristics for starch hydrogels elaboration. The objective of this study was to evaluate the influence of amylose content and the gelatinization method on the physicochemical characteristics of native and cross-linked rice starch hydrogels. The native and cross-linked starches were gelatinized with heating or alkaline solution, added polyvinyl alcohol, frozen and then freeze-dried. The cross-linked starch had a low final viscosity (101.38 RVU), which made the heat-induced gelatinized hydrogel readily disintegrated in water. However, modified starch hydrogels obtained by alkaline-induced gelatinization resulted in a more rigid structure than the native starch hydrogels. In addition, the starch sample with high amylose content had lower water absorption (322.2%) due to the greater stiffness of the hydrogel structure that resisted swelling. The alkaline-gelatinization resulted in stiffer hydrogels with lower water absorption (322.2 to 534.8%), while the heat-gelatinized behaved as a superabsorbent (658.7 to 1068.5%). The variability of the hydrogels properties of this study can enable a range of applications due to different amylose contents and gelatinization methods. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of visible-light responsive and mechanically enhanced "smart" UCST interpenetrating network hydrogels.

PubMed

Xu, Yifei; Ghag, Onkar; Reimann, Morgan; Sitterle, Philip; Chatterjee, Prithwish; Nofen, Elizabeth; Yu, Hongyu; Jiang, Hanqing; Dai, Lenore L

2017-12-20

An interpenetrating polymer network (IPN), chlorophyllin-incorporated environmentally responsive hydrogel was synthesized and exhibited the following features: enhanced mechanical properties, upper critical solution temperature (UCST) swelling behavior, and promising visible-light responsiveness. Poor mechanical properties are known challenges for hydrogel-based materials. By forming an interpenetrating network between polyacrylamide (PAAm) and poly(acrylic acid) (PAAc) polymer networks, the mechanical properties of the synthesized IPN hydrogels were significantly improved compared to hydrogels made of a single network of each polymer. The formation of the interpenetrating network was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), the analysis of glass transition temperature, and a unique UCST responsive swelling behavior, which is in contrast to the more prevalent lower critical solution temperature (LCST) behaviour of environmentally responsive hydrogels. The visible-light responsiveness of the synthesized hydrogel also demonstrated a positive swelling behavior, and the effect of incorporating chlorophyllin as the chromophore unit was observed to reduce the average pore size and further enhance the mechanical properties of the hydrogel. This interpenetrating network system shows potential to serve as a new route in developing "smart" hydrogels using visible-light as a simple, inexpensive, and remotely controllable stimulus.

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

Structure and mechanical properties of supramolecular random copolymer hydrogels cross linked by hydrophobic aggregates.

NASA Astrophysics Data System (ADS)

Vogt, Bryan; Wiener, Clinton; Wang, Chao; Weiss, Bob

Stress dissipation mechanisms are critical to improving the toughness of hydrogels. The use of reversible hydrophobic associations for crosslnking of hydrogels provides such a mechanism for toughening, but can also lead to the creep of the hydrogel as the crosslinks break and reform. The morphology of the hydrophobic aggregates thus is critical to the mechanical properties of the hydrogels. In this work, we will demonstrate how the processing of these copolymers impacts the hydrogel structure and this structure is correlated with the mechanical properties through a combination of small angle scattering, rheology, and tensile measurements. The hydrophilic and hydrophobic chemistries in the copolymer can be used to tune the water content and strength of the crosslinks, while the copolymer composition provides the number density of crosslinks and also acts to modulate the swelling of the hydrogel. These copolymers as well as their hydrogels can in general use traditional polymer processing, but the details of this processing impacts both the nanoscale morphology and the resultant mechanical properties of the hydrogels. This work was financially supported by the Civil, Mechanical and Manufacturing Innovation (CMMI) Division in the Directorate for Engineering of the National Science Foundation, Grant. CMMI-1300212.

An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering

NASA Astrophysics Data System (ADS)

Chen, Feng; Yu, Songrui; Liu, Bing; Ni, Yunzhou; Yu, Chunyang; Su, Yue; Zhu, Xinyuan; Yu, Xiaowei; Zhou, Yongfeng; Yan, Deyue

2016-01-01

In this study, an enzymatically cross-linked injectable and biodegradable hydrogel system comprising carboxymethyl pullulan-tyramine (CMP-TA) and chondroitin sulfate-tyramine (CS-TA) conjugates was successfully developed under physiological conditions in the presence of both horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) for cartilage tissue engineering (CTTE). The HRP crosslinking method makes this injectable system feasible, minimally invasive and easily translatable for regenerative medicine applications. The physicochemical properties of the mechanically stable hydrogel system can be modulated by varying the weight ratio and concentration of polymer as well as the concentrations of crosslinking reagents. Additionally, the cellular behaviour of porcine auricular chondrocytes encapsulated into CMP-TA/CS-TA hydrogels demonstrates that the hydrogel system has a good cyto-compatibility. Specifically, compared to the CMP-TA hydrogel, these CMP-TA/CS-TA composite hydrogels have enhanced cell proliferation and increased cartilaginous ECM deposition, which significantly facilitate chondrogenesis. Furthermore, histological analysis indicates that the hydrogel system exhibits acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable pullulan/chondroitin sulfate composite hydrogels presented here are expected to be useful biomaterial scaffold for regenerating cartilage tissue.

Subconjunctivally Implantable Hydrogels with Degradable and Thermoresponsive Properties for Sustained Release of Insulin to the Retina

PubMed Central

Misra, Gauri P.; Singh, Ravi S.J.; Aleman, Tomas S.; Jacobson, Samuel G.; Gardner, Thomas W.; Lowe, Tao L.

2009-01-01

The objective of this work is to develop subconjunctivally implantable, biodegradable hydrogels for sustained release of intact insulin to the retina to prevent and treat retinal neurovascular degeneration such as diabetic retinopathy. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide (NIPAAm) monomer and a dextran macromer containing multiple hydrolytically degradable oligolactate-(2-hydroxyetheyl methacrylate) units (Dex-lactateHEMA) in 25:75 (v:v) ethanol:water mixture solvent. Insulin is loaded into the hydrogels during the synthesis process with loading efficiency up to 98%. The hydrogels can release biologically active insulin in vitro for at least one week and the release kinetics can be modulated by varying the ratio between NIPAAm and Dex-lactateHEMA and altering the physical size of the hydrogels. The hydrogels are not toxic to R28 retinal neuron cells in culture medium with 100% cell viability. The hydrogels can be implanted under the conjunctiva without causing adverse effects to the retina based on hematoxylin and eosin stain, immunostaining for microglial cell activation, and electroretinography. These subconjunctivally implantable hydrogels have potential for long-term periocular delivery of insulin or other drugs to treat diabetic retinopathy and other retinal diseases. PMID:19709741

Heparin-based hydrogels with tunable sulfation & degradation for anti-inflammatory small molecule delivery.

PubMed

Peng, Yifeng; Tellier, Liane E; Temenoff, Johnna S

2016-08-16

Sustained release of anti-inflammatory agents remains challenging for small molecule drugs due to their low molecular weight and hydrophobicity. Therefore, the goal of this study was to control the release of a small molecule anti-inflammatory agent, crystal violet (CV), from hydrogels fabricated with heparin, a highly sulfated glycosaminoglycan capable of binding positively-charged molecules such as CV. In this system, both electrostatic interactions between heparin and CV and hydrogel degradation were tuned simultaneously by varying the level of heparin sulfation and varying the amount of dithiothreitol within hydrogels, respectively. It was found that heparin sulfation significantly affected CV release, whereby more sulfated heparin hydrogels (Hep and Hep(-N)) released CV with near zero-order release kinetics (R-squared values between 0.96-0.99). Furthermore, CV was released more quickly from fast-degrading hydrogels than slow-degrading hydrogels, providing a method to tune total CV release between 5-15 days while maintaining linear release kinetics. In particular, N-desulfated heparin hydrogels exhibited efficient CV loading (∼90% of originally included CV), near zero-order CV release kinetics, and maintenance of CV bioactivity after release, making this hydrogel formulation a promising CV delivery vehicle for a wide range of inflammatory diseases.

Temperature responsive hydrogel magnetic nanocomposites for hyperthermia and metal extraction applications

NASA Astrophysics Data System (ADS)

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

2015-11-01

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

Superabsorbent hydrogel composite based on copolymer cellulose/poly (vinyl alcohol)/CNT

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

Khoerunnisa, Fitri, E-mail: fitri.khoerunnisa@gmail.com; Hendrawan,; Sonjaya, Yaya

2016-04-19

Superabsorbent hydrogels are cross-linked hydrophilic polymers that can absorb and retain a large volume of water, saline solution, or physiological fluids. A distinctive superabsorbent hydrogel composite based on cellulose/ poly (vinyl alcohol)/ carbon nanotubes was successfully synthesized via the graft bio-copolymerization in an aqueous medium with glutaraldehide as a crosslinking agent. The effect of carbon nanotubes (CNT) on water absorption capacity and mechanical properties of superabsorbent composite were particularly investigated. The Fourier transform infrared spectra showed the evidence of copolymerization of hydrogel precursors as well as the interaction of CNT filler with the hydrogel matrices, as indicated by the shiftingmore » of peak intensity and position of several functional groups (O-H, C-H sp{sup 3}, C=O, C-N, C-O). The modification of hydrogel surface morphology and porosity owing to CNT insertion was also confirmed by scanning electron microscopy images. The CNT insertion improved the mechanical strength of superabsorbent hydrogel composites. Moreover, insertion of CNT into hydrogel matrix remarkably increased the swelling capacity of superabsorbent composites up to 840%. This huge water absorption capacity of hydrogel composites offers promising applications in development of superabsorbent polymers.« less

The Formation Mechanism of Hydrogels.

PubMed

Lu, Liyan; Yuan, Shiliang; Wang, Jing; Shen, Yun; Deng, Shuwen; Xie, Luyang; Yang, Qixiang

2017-06-12

Hydrogels are degradable polymeric networks, in which cross-links play a vital role in structure formation and degradation. Cross-linking is a stabilization process in polymer chemistry that leads to the multi-dimensional extension of polymeric chains, resulting in network structures. By cross-linking, hydrogels are formed into stable structures that differ from their raw materials. Generally, hydrogels can be prepared from either synthetic or natural polymers. Based on the types of cross-link junctions, hydrogels can be categorized into two groups: the chemically cross-linked and the physically cross-linked. Chemically cross-linked gels have permanent junctions, in which covalent bonds are present between different polymer chains, thus leading to excellent mechanical strength. Although chemical cross-linking is a highly resourceful method for the formation of hydrogels, the cross-linkers used in hydrogel preparation should be extracted from the hydrogels before use, due to their reported toxicity, while, in physically cross-linked gels, dissolution is prevented by physical interactions, such as ionic interactions, hydrogen bonds or hydrophobic interactions. Physically cross-linked methods for the preparation of hydrogels are the alternate solution for cross-linker toxicity. Both methods will be discussed in this essay. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction

PubMed Central

Khattab, Ahmad; Islam, Mohammad Ariful; Hweij, Khaled Abou; Zeitouny, Joya; Waters, Renae; Sayegh, Malek; Hossain, Md Monowar; Paul, Arghya

2015-01-01

Cardiac tissue damage due to myocardial infarction (MI) is one of the leading causes of mortality worldwide. The available treatments of MI include pharmaceutical therapy, medical device implants, and organ transplants, all of which have severe limitations including high invasiveness, scarcity of donor organs, thrombosis or stenosis of devices, immune rejection, and prolonged hospitalization time. Injectable hydrogels have emerged as a promising solution for in situ cardiac tissue repair in infarcted hearts after MI. In this review, an overview of various natural and synthetic hydrogels for potential application as injectable hydrogels in cardiac tissue repair and regeneration is presented. The review starts with brief discussions about the pathology of MI, its current clinical treatments and their limitations, and the emergence of injectable hydrogels as a potential solution for post MI cardiac regeneration. It then summarizes various hydrogels, their compositions, structures and properties for potential application in post MI cardiac repair, and recent advancements in the application of injectable hydrogels in treatment of MI. Finally, the current challenges associated with the clinical application of injectable hydrogels to MI and their potential solutions are discussed to help guide the future research on injectable hydrogels for translational therapeutic applications in regeneration of cardiac tissue after MI. PMID:27668147

Hydrogel Macroporosity and the Prolongation of Transgene Expression and the Enhancement of Angiogenesis

PubMed Central

Shepard, Jaclyn A.; Virani, Farrukh R.; Goodman, Ashley G.; Gossett, Timothy D.; Shin, Seungjin; Shea, Lonnie D.

2012-01-01

The utility of hydrogels for regenerative medicine can be improved through localized gene delivery to enhance their bioactivity. However, current systems typically lead to low-level transgene expression located in host tissue surrounding the implant. Herein, we investigated the inclusion of macropores into hydrogels to facilitate cell ingrowth and enhance gene delivery within the macropores in vivo. Macropores were created within PEG hydrogels by gelation around gelatin microspheres, with gelatin subsequently dissolved by incubation at 37°C. The macropores were interconnected, as evidenced by homogeneous cell seeding in vitro and complete cell infiltration in vivo. Lentivirus loaded within hydrogels following gelation retained its activity relative to the unencapsulated control virus. In vivo, macroporous PEG demonstrated sustained, elevated levels of transgene expression for 6 weeks, while hydrogels without macropores had transient expression. Transduced cells were located throughout the macroporous structure, while non-macroporous PEG hydrogels had transduction only in the adjacent host tissue. Delivery of lentivirus encoding for VEGF increased vascularization relative to the control, with vessels throughout the macropores of the hydrogel. The inclusion of macropores within the hydrogel to enhance cell infiltration enhances transduction and influences tissue development, which has implications for multiple regenerative medicine applications. PMID:22800542

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

PubMed

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

2017-08-01

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

A postoperative anti-adhesion barrier based on photoinduced imine-crosslinking hydrogel with tissue-adhesive ability.

PubMed

Yang, Yunlong; Liu, Xiaolin; Li, Yan; Wang, Yang; Bao, Chunyan; Chen, Yunfeng; Lin, Qiuning; Zhu, Linyong

2017-10-15

Postoperative adhesion is a serious complication that can further lead to morbidity and/or mortality. Polymer anti-adhesion barrier material provides an effective precaution to reduce the probability of postoperative adhesion. Clinical application requires these materials to be easily handled, biocompatible, biodegradable, and most importantly tissue adherent to provide target sites with reliable isolation. However, currently there is nearly no polymer barrier material that can fully satisfy these requirements. In this study, based on the photoinduced imine-crosslinking (PIC) reaction, we had developed a photo-crosslinking hydrogel (CNG hydrogel) that composed of o-nitrobenzyl alcohol (NB) modified carboxymethyl cellulose (CMC-NB) and glycol chitosan (GC) as an anti-adhesion barrier material. Under light irradiation, CMC-NB generated aldehyde groups which subsequently reacted with amino groups distributed on GC or tissue surface to form a hydrogel barrier that covalently attached to tissue surface. Rheological analysis demonstrated that CNG hydrogel (30mg/mL polymer content) could be formed in 30s upon light irradiation. Tissue adhesive tests showed that the tissue adhesive strength of CNG hydrogel (30mg/mL) was about 8.32kPa-24.65kPa which increased with increasing CMC-NB content in CNG hydrogel. Toxicity evaluation by L929 cells demonstrated that CNG hydrogel was cytocompatible. Furthermore, sidewall defect-cecum abrasion model of rat was employed to evaluate the postoperative anti-adhesion efficacy of CNG hydrogel. And a significantly reduction of tissue adhesion (20% samples with low score adhesion) was found in CNG hydrogel treated group, compared with control group (100% samples with high score adhesion). In addition, CNG hydrogel could be degraded in nearly 14days and showed no side effect on wound healing. These findings indicated that CNG hydrogel can effectively expanded the clinical treatments of postoperative tissue adhesion. In this study, a tissue adhesive photo-crosslinking hydrogel (CNG) was developed based on photo-induced imine crosslinking reaction (PIC) for postoperative anti-adhesion. CNG hydrogel showed the features of easy and convenient operation, fast and controllable gelation, suitable gel strength, good biocompatibility, and most importantly strong tissue adhesiveness. Therefore, it shows very high performance to prevent postoperative tissue adhesion. Overall, our study provides a more suitable hydrogel barrier material that can overcome the shortcomings of current barriers for clinical postoperative anti-adhesion. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of hydrogel elasticity and ephrinB2-immobilized manner on Runx2 expression of human mesenchymal stem cells.

PubMed

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

2017-08-01

The objective of this study is to design the manner of ephrinB2 immobilized onto polyacrylamide (PAAm) hydrogels with varied elasticity and evaluate the effect of hydrogels elasticity and the immobilized manner of ephrinB2 on the Runx2 expression of human mesenchymal stem cells (hMSC). The PAAm hydrogels were prepared by the radical polymerization of acrylamide (AAm), and N,N'-methylenebisacrylamide (BIS). By changing the BIS concentration, the elasticity of PAAm hydrogels changed from 1 to 70kPa. For the bio-specific immobilization of ephrinB2, a chimeric protein of ephrinB2 and Fc domain was immobilized onto protein A-conjugated PAAm hydrogels by making use of the bio-specific interaction between the Fc domain and protein A. When hMSC were cultured on the ephrinB2-immobilized PAAm hydrogels with varied elasticity, the morphology of hMSC was of cuboidal shape on the PAAm hydrogels immobilized with ephrinB2 compared with non-conjugated ones, irrespective of the hydrogels elasticity. The bio-specific immobilization of ephrinB2 enhanced the level of Runx2 expression. The expression level was significantly high for the hydrogels of 3.6 and 5.9kPa elasticity with bio-specific immobilization of ephrinB2 compared with other hydrogels with the same elasticity. The hydrogels showed a significantly down-regulated RhoA activity. It is concluded that the Runx2 expression of hMSC is synergistically influenced by the hydrogels elasticity and their immobilized manner of ephrinB2 immobilized. Differentiation fate of mesenchymal stem cells (MSC) is modified by biochemical and biophysical factors, such as elasticity and signal proteins. However, there are few experiments about combinations of them. In this study, to evaluate the synergistic effect of them on cell properties of MSC, we established to design the manner of Eph signal ligand, ephrinB2, immobilized onto polyacrylamide hydrogels with varied elasticity. The gene expression level of an osteogenic maker, Runx2, was enhanced by the immobilized manner, and significantly enhanced for the hydrogels of around 4kPa elasticity with bio-specific immobilization of ephrinB2. This is the novel report describing to demonstrate that the Runx2 expression of MSC is synergistically influenced by the hydrogels elasticity and their manner of ephrinB2 immobilized. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-09-01

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

Platelet-rich plasma loaded in situ-formed hydrogel enhances hyaline cartilage regeneration by CB1 upregulation.

PubMed

Lee, Hye-Rim; Park, Kyung Min; Joung, Yoon Ki; Park, Ki Dong; Do, Sun Hee

2012-11-01

The efficacy of three-dimensional (3D) culture on the proliferation and maturation of chondrocytes seeded into a hydrogel scaffold was assessed. Three types of hydrogel were prepared for the 3D culture of primary isolated chondrocytes. Chondrocyte proliferation was assessed using a live/dead viability/cytotoxicity assay and semiquantitative RT-PCR after 3D culture in hydrogel. Cylindrical defects in the center of rat xyphoids were used for the implantation of platelet-rich plasma (PRP)/hydrogel composites. Rats were killed at day 7 postoperatively and evaluated histochemically and immunohistologically. Xyphoid chondrocytes proliferated well with time in hydrogels. In the PRP-containing hydrogels, xyphoid defects displayed early formation of chondroid matrix with massive peripheral infiltration of spindle cells. These results were consistent with Safranin-O staining for proteoglycans and immunohistochemistry for type II collagen. Gene expression analyses in vitro revealed aggrecan, type II collagen, and ChM-1 and CB1 upregulation by PRP/hydrogel. PRP/hydrogel provided a suitable environment for hyaline cartilaginous regeneration, leading to anti-inflammation by significant increase of CB1 and inhibiting vascular ingrowth via considerable upregulation of ChM-1. The results provide a valuable reference for the clinical application of hydrogel scaffolds for hyaline cartilage regeneration, as well as the use of autologous PRP to improve cellular proliferation and maturation of xyphoid repair. Copyright © 2012 Wiley Periodicals, Inc.

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

PubMed

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

2017-08-01

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

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

PubMed

Son, Kuk Hui; Lee, Jin Woo

2016-10-20

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

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

PubMed

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

2012-08-01

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

Soft contact lens biomaterials from bioinspired phospholipid polymers.

PubMed

Goda, Tatsuro; Ishihara, Kazuhiko

2006-03-01

Soft contact lens (SCL) biomaterials originated from the discovery of a poly(2-hydroxyethyl methacrylate) (poly[HEMA])-based hydrogel in 1960. Incorporation of hydrophilic polymers into poly(HEMA) hydrogels was performed in the 1970-1980s, which brought an increase in the equilibrium water content, leading to an enhancement of the oxygen permeability. Nowadays, the poly(HEMA)-based hydrogels have been applied in disposable SCL. At the same time, high oxygen-permeable silicone hydrogels were produced, which made it possible to continually wear SCL. Recently, numerous trials for improving the water wettability of silicone hydrogels have been performed. However, little attention has been paid to improving their anti-biofouling properties and biocompatibility. Since biomimetic phospholipid polymers possess excellent anti-biofouling properties and biocompatibility they have the potential to play a valuable role in the surface modification of the silicone hydrogel. The representative phospholipid polymers containing a 2-methacryloyloxyethyl phosphorylcholine (MPC) unit suppressed nonspecific protein adsorption, increased cell compatibility and contributed to blood compatible biomaterials. The MPC polymer coating on the silicone hydrogel improved its water wettability and biocompatibility, while maintaining high oxygen permeability compared with the original silicone hydrogel. Furthermore, the newly prepared phospholipid-type intermolecular crosslinker made it possible to synthesize a 100% phospholipid polymer hydrogel that can enhance the anti-biofouling properties and biocompatibility. In this review, the authors discuss how polymer hydrogels should be designed in order to obtain a biocompatible SCL and future perspectives.

Tribological properties of PVA/PVP blend hydrogels against articular cartilage.

PubMed

Kanca, Yusuf; Milner, Piers; Dini, Daniele; Amis, Andrew A

2018-02-01

This research investigated in-vitro tribological performance of the articulation of cartilage-on- polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) blend hydrogels using a custom-designed multi-directional wear rig. The hydrogels were prepared by repeated freezing-thawing cycles at different concentrations and PVA to PVP fractions at a given concentration. PVA/PVP blend hydrogels showed low coefficient of friction (COF) values (between 0.12 ± 0.01 and 0.14 ± 0.02) which were closer to the cartilage-on-cartilage articulation (0.03 ± 0.01) compared to the cartilage-on-stainless steel articulation (0.46 ± 0.06). The COF increased with increasing hydrogel concentration (p = 0.03) and decreasing PVP content at a given concentration (p < 0.05). The cartilage-on-hydrogel tests showed only the surface layers of the cartilage being removed (average volume loss of the condyles was 12.5 ± 4.2mm 3 ). However, the hydrogels were found to be worn/deformed. The hydrogels prepared at a higher concentration showed lower apparent volume loss. A strong correlation (R 2 = 0.94) was found between the COF and compressive moduli of the hydrogel groups, resulting from decreasing contact congruency. It was concluded that the hydrogels were promising as hemiarthroplasty materials, but that improved mechanical behaviour was required for clinical use. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-01-21

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

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

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

Self-assembly of cationic multidomain peptide hydrogels: supramolecular nanostructure and rheological properties dictate antimicrobial activity

NASA Astrophysics Data System (ADS)

Jiang, Linhai; Xu, Dawei; Sellati, Timothy J.; Dong, He

2015-11-01

Hydrogels are an important class of biomaterials that have been widely utilized for a variety of biomedical/medical applications. The biological performance of hydrogels, particularly those used as wound dressing could be greatly advanced if imbued with inherent antimicrobial activity capable of staving off colonization of the wound site by opportunistic bacterial pathogens. Possessing such antimicrobial properties would also protect the hydrogel itself from being adversely affected by microbial attachment to its surface. We have previously demonstrated the broad-spectrum antimicrobial activity of supramolecular assemblies of cationic multi-domain peptides (MDPs) in solution. Here, we extend the 1-D soluble supramolecular assembly to 3-D hydrogels to investigate the effect of the supramolecular nanostructure and its rheological properties on the antimicrobial activity of self-assembled hydrogels. Among designed MDPs, the bactericidal activity of peptide hydrogels was found to follow an opposite trend to that in solution. Improved antimicrobial activity of self-assembled peptide hydrogels is dictated by the combined effect of supramolecular surface chemistry and storage modulus of the bulk materials, rather than the ability of individual peptides/peptide assemblies to penetrate bacterial cell membrane as observed in solution. The structure-property-activity relationship developed through this study will provide important guidelines for designing biocompatible peptide hydrogels with built-in antimicrobial activity for various biomedical applications.Hydrogels are an important class of biomaterials that have been widely utilized for a variety of biomedical/medical applications. The biological performance of hydrogels, particularly those used as wound dressing could be greatly advanced if imbued with inherent antimicrobial activity capable of staving off colonization of the wound site by opportunistic bacterial pathogens. Possessing such antimicrobial properties would also protect the hydrogel itself from being adversely affected by microbial attachment to its surface. We have previously demonstrated the broad-spectrum antimicrobial activity of supramolecular assemblies of cationic multi-domain peptides (MDPs) in solution. Here, we extend the 1-D soluble supramolecular assembly to 3-D hydrogels to investigate the effect of the supramolecular nanostructure and its rheological properties on the antimicrobial activity of self-assembled hydrogels. Among designed MDPs, the bactericidal activity of peptide hydrogels was found to follow an opposite trend to that in solution. Improved antimicrobial activity of self-assembled peptide hydrogels is dictated by the combined effect of supramolecular surface chemistry and storage modulus of the bulk materials, rather than the ability of individual peptides/peptide assemblies to penetrate bacterial cell membrane as observed in solution. The structure-property-activity relationship developed through this study will provide important guidelines for designing biocompatible peptide hydrogels with built-in antimicrobial activity for various biomedical applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05233e

Hydrogel Walkers with Electro-Driven Motility for Cargo Transport.

PubMed

Yang, Chao; Wang, Wei; Yao, Chen; Xie, Rui; Ju, Xiao-Jie; Liu, Zhuang; Chu, Liang-Yin

2015-08-28

In this study, soft hydrogel walkers with electro-driven motility for cargo transport have been developed via a facile mould-assisted strategy. The hydrogel walkers consisting of polyanionic poly(2-acrylamido-2-methylpropanesulfonic acid-co-acrylamide) exhibit an arc looper-like shape with two "legs" for walking. The hydrogel walkers can reversibly bend and stretch via repeated "on/off" electro-triggers in electrolyte solution. Based on such bending/stretching behaviors, the hydrogel walkers can move their two "legs" to achieve one-directional walking motion on a rough surface via repeated "on/off" electro-triggering cycles. Moreover, the hydrogel walkers loaded with very heavy cargo also exhibit excellent walking motion for cargo transport. Such hydrogel systems create new opportunities for developing electro-controlled soft systems with simple design/fabrication strategies in the soft robotic field for remote manipulation and transportation.

The composite hydrogels of polyvinyl alcohol-gellan gum-Ca(2+) with improved network structure and mechanical property.

PubMed

Wang, Fei; Wen, Ying; Bai, Tongchun

2016-12-01

The composite hydrogels of polyvinyl alcohol (PVA) and gellan gum (GG) are of interesting in the biomaterials application. To improve the structure and mechanical property, in this work, Ca(2+) ion was introduced to crosslink the polymer chain, and the PVA-GG-Ca(2+) hydrogel was formed. By analyzing its structure, mechanical properties, swelling and dehydration kinetics, the effect of molecular interaction on hydrogel structure and properties have been observed. Our result indicates that, as GG is added to hydrogel network, the role of Ca(2+) ion is stand out, it reorganizes the network structure, enhances the mechanical properties, and strengthens the electrolytic and hydrogen bonding interactions in PVA-GG-Ca(2+) hydrogels. These observations will benefit the development of hydrogels in biomaterials application. Copyright © 2016. Published by Elsevier B.V.

Hydrogels for Engineering of Perfusable Vascular Networks

PubMed Central

Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S. P.; Machens, Hans-Günther; Schilling, Arndt F.

2015-01-01

Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation. PMID:26184185

Fluorescent Dendritic Micro-Hydrogels: Synthesis, Analysis and Use in Single-Cell Detection.

PubMed

Christadore, Lisa; Grinstaff, Mark W; Schaus, Scott E

2018-04-18

Hydrogels are of keen interest for a wide range of medical and biotechnological applications including as 3D substrate structures for the detection of proteins, nucleic acids, and cells. Hydrogel parameters such as polymer wt % and crosslink density are typically altered for a specific application; now, fluorescence can be incorporated into such criteria by specific macromonomer selection. Intrinsic fluorescence was observed at λ max 445 nm from hydrogels polymerized from lysine and aldehyde- terminated poly(ethylene glycol) macromonomers upon excitation with visible light. The hydrogel’s photochemical properties are consistent with formation of a nitrone functionality. Printed hydrogels of 150 μm were used to detect individual cell adherence via a decreased in fluorescence. The use of such intrinsically fluorescent hydrogels as a platform for cell sorting and detection expands the current repertoire of tools available.

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

PubMed

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

2017-12-22

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

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

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

Andarini, Mellissa; Lazim, Azwan

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

Free radical scavenging injectable hydrogels for regenerative therapy.

PubMed

Komeri, Remya; Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2017-02-01

Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Controlled release of paclitaxel from a self-assembling peptide hydrogel formed in situ and antitumor study in vitro

PubMed Central

Liu, Jingping; Zhang, Lanlan; Yang, Zehong; Zhao, Xiaojun

2011-01-01

Background A nanoscale injectable in situ-forming hydrogel drug delivery system was developed in this study. The system was based on a self-assembling peptide RADA16 solution, which can spontaneously form a hydrogel rapidly under physiological conditions. We used the RADA16 hydrogel for the controlled release of paclitaxel (PTX), a hydrophobic antitumor drug. Methods The RADA16-PTX suspension was prepared simply by magnetic stirring, followed by atomic force microscopy, circular dichroism analysis, dynamic light scattering, rheological analysis, an in vitro release assay, and a cell viability test. Results The results indicated that RADA16 and PTX can interact with each other and that the amphiphilic peptide was able to stabilize hydrophobic drugs in aqueous solution. The particle size of PTX was markedly decreased in the RADA16 solution compared with its size in water. The RADA16-PTX suspension could form a hydrogel in culture medium, and the elasticity of the hydrogel showed a positive correlation with peptide concentration. In vitro release measurements indicated that hydrogels with a higher peptide concentration had a longer half-release time. The RADA16-PTX hydrogel could effectively inhibit the growth of the breast cancer cell line, MDA-MB-435S, in vitro, and hydrogels with higher peptide concentrations were more effective at inhibiting tumor cell proliferation. The RADA16-PTX hydrogel was effective at controlling the release of PTX and inhibiting tumor cell growth in vitro. Conclusion Self-assembling peptide hydrogels may work well as a system for drug delivery. PMID:22114478

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

PubMed Central

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

2017-01-01

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

Mechanical and transport properties of the poly(ethylene oxide)-poly(acrylic acid) double network hydrogel from molecular dynamic simulations.

PubMed

Jang, Seung Soon; Goddard, William A; Kalani, M Yashar S

2007-02-22

We used atomistic molecular dynamics (MD) simulations to investigate the mechanical and transport properties of the PEO-PAA double network (DN) hydrogel with 76 wt % water content. By analyzing the pair correlation functions for polymer-water pairs and for ion-water pairs and the solvent accessible surface area, we found that the solvation of polymer and ion in the DN hydrogel is enhanced in comparison with both PEO and PAA single network (SN) hydrogels. The effective mesh size of this DN hydrogel is smaller than that of the SN hydrogels with the same water content and the same molecular weight between the cross-linking points (Mc). Applying uniaxial extensions, we obtained the stress-strain curves for the hydrogels. This shows that the DN hydrogel has a sudden increase of stress above approximately 100% strain, much higher than the sum of the stresses of the two SN hydrogels at the same strain. This arises because PEO has a smaller Mc value than PAA, so that the PEO in the DN reaches fully stretched out at 100% strain that corresponds to 260% strain in the PEO SN (beyond this point, the bond stretching and the angle bending increase dramatically). We also calculated the diffusion coefficients of solutes such as D-glucose and ascorbic acid in the hydrogels, where we find that the diffusion coefficients of those solutes in the DN hydrogel are 60% of that in the PEO SN and 40% of that in the PAA SN due to its smaller effective mesh size.

Core-shell silk hydrogels with spatially tuned conformations as drug-delivery system.

PubMed

Yan, Le-Ping; Oliveira, Joaquim M; Oliveira, Ana L; Reis, Rui L

2017-11-01

Hydrogels of spatially controlled physicochemical properties are appealing platforms for tissue engineering and drug delivery. In this study, core-shell silk fibroin (SF) hydrogels of spatially controlled conformation were developed. The core-shell structure in the hydrogels was formed by means of soaking the preformed (enzymatically crosslinked) random coil SF hydrogels in methanol. When increasing the methanol treatment time from 1 to 10 min, the thickness of the shell layer can be tuned from about 200 to about 850 μm as measured in wet status. After lyophilization of the rehydrated core-shell hydrogels, the shell layer displayed compact morphology and the core layer presented porous structure, when observed by scanning electron microscopy. The conformation of the hydrogels was evaluated by Fourier transform infrared spectroscopy in wet status. The results revealed that the shell layer possessed dominant β-sheet conformation and the core layer maintained mainly random coil conformation. Enzymatic degradation data showed that the shell layers presented superior stability to the core layer. The mechanical analysis displayed that the compressive modulus of the core-shell hydrogels ranged from about 25 kPa to about 1.1 MPa by increasing the immersion time in methanol. When incorporated with albumin, the core-shell SF hydrogels demonstrated slower and more controllable release profiles compared with the non-treated hydrogel. These core-shell SF hydrogels of highly tuned properties are useful systems as drug-delivery system and may be applied as cartilage substitute. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Synthesis and preparation of biodegradable hybrid dextran hydrogel incorporated with biodegradable curcumin nanomicelles for full thickness wound healing.

PubMed

Alibolandi, Mona; Mohammadi, Marzieh; Taghdisi, Seyed Mohammad; Abnous, Khalil; Ramezani, Mohammad

2017-10-30

There is a clinical need for a novel, more efficient therapy for full thickness wound healing. In the current study, curcumin encapsulated PEG-PLA [poly(lactide)-block-poly(ethylene glycol)] nanomicelles were incorporated into dextran hydrogel for a full thickness dermal wound healing application. To assess the application of the hydrogel as a therapeutic wound dressing, its morphology, swelling pattern, kinetics of degradation, and capacity to control curcumin release were evaluated. It was found that the prepared hybrid hydrogel had acceptable biocompatibility, incorporation capacity of curcumin nanomicelles, and mechanical properties. An in vitro release experiment also demonstrated the sustained release of curcumin from dextran hydrogel, which was first controlled by the diffusion of curcumin from hydrogel and continued through hydrogel matrix erosion at the terminal phase. An in vivo wound healing experiment was carried out using dressing hydrogels on full thickness wounds in BALB/c mice. An histological study demonstrated that the application of curcumin nanomicelles incorporated hydrogel could significantly augment the re-epithelialization of epidermis and collagen deposition in the wound area. Expression of CD31 and vimentin in wound tissue was investigated using immunohistochemistry tests on the eighth day post wounding. The results obtained demonstrated that curcumin nanomicelles incorporated hydrogel could significantly accelerate angiogenesis, fibroblast accumulation, and the process of wound healing. Together, the data indicate that the prepared hybrid curcumin PEG-PLA nanomicelles incorporated dextran hydrogel is a promising candidate for full thickness wound treatment that increases re-epithelialization, collagen deposition, angiogenesis, and tissue granulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Photothermal fabrication of microscale patterned DNA hydrogels

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Phase 2 Studies: Impacts of Commercial Navigation Traffic on Freshwater Mussels at the W.H. Zimmer Station, 1989-90 Baseline Studies

DTIC Science & Technology

1991-09-01

eds. 215-273. New York: Academic Press. Green, R . H. 1979. Sampling design and statistical methods for environ- mental biologists. New York: John ...Station, Corps of Engineers 3909 Halls Ferry Road, Vicksburg. Mississippi 39180-6199 f’ F rr is RWA~ September1991 Final Report p, r l , . . 91-16950...was provided by Mr. Scott Schermerhorn , Ms. Cheryl Tansky, and Dr. Albert Burky, all with the University of Dayton, and Ms. Sarah Wilkerson, WES Dr

CAIRSENSE-Atlanta

EPA Pesticide Factsheets

Short time interval comparisons of low cost sensor response and corresponding Federal Reference or Federal Equivalent Monitors at an NCOR site located in proximity to Atlanta, GeorgiaThis dataset is associated with the following publication:Jiao, W., G. Hagler, R. Williams, R. Sharpe, R. Brown, D. Garver, R. Judge, M. Caudill, J. Rickard, M. Davis, L. Weinstock, S. Zimmer-Dauphinee, and K. Buckley. Community Air Sensor Network (CAIRSENSE) project: Evaluation of low-cost sensor performance in a suburban environment in the southeastern United States. Atmospheric Measurement Techniques. Copernicus Publications, Katlenburg-Lindau, GERMANY, 9: 5282-5292, (2016).

Low-temperature fabrication of 3D drilled graphene sheets hydrogel for supercapacitors with ultralong cycle life

NASA Astrophysics Data System (ADS)

Qiu, Zenghui; He, Dawei; Wang, Yongsheng; Li, Jiayuan

2017-09-01

A simple cobalt catalyzed gasification strategy to synthesize drilled graphene sheets (DGNs) is performed, and 3D DGNs hydrogel is prepared at a relatively low temperature. Due to mesopore hydrogel structure that increases the charge transfer efficiency by providing pathways for ionic into the overlaps of DGNs hydrogel and hole density displays controllably, the resulting DGNs hydrogel electrode provides excellent rate capability with an ultrahigh specific capacitance of 264.1 F g-1 at 1 A g-1 compared to a value of 187.8 F g-1 for graphene sheets (GNs) pole. DGNs hydrogel expands the design space for developing high-performance energy storage devices.

Hybrid hydrogels produced by ionizing radiation technique

NASA Astrophysics Data System (ADS)

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

2012-09-01

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

Dual drug release from hydrogels covalently containing polymeric micelles that possess different drug release properties.

PubMed

Murata, Mari; Uchida, Yusuke; Takami, Taku; Ito, Tomoki; Anzai, Ryosuke; Sonotaki, Seiichi; Murakami, Yoshihiko

2017-05-01

In the present study, we designed hydrogels for dual drug release: the hydrogels that covalently contained the polymeric micelles that possess different drug release properties. The hydrogels that were formed from polymeric micelles possessing a tightly packed (i.e., well-entangled) inner core exhibited a higher storage modulus than the hydrogels that were formed from the polymeric micelles possessing a loosely packed structure. Furthermore, we conducted release experiments and fluorescent observations to evaluate the profiles depicting the release of two compounds, rhodamine B and auramine O, from either polymeric micelles or hydrogels. According to our results, (1) hydrogels that covalently contains polymeric micelles that possess different drug release properties successfully exhibit the independent release behaviors of the two compounds and (2) fluorescence microscopy can greatly facilitate efforts to evaluate drug release properties of materials. Copyright © 2017 Elsevier B.V. All rights reserved.