Viscosity Of Hydrogel Research Articles

Holmium-Containing Bioactive Glasses Dispersed in Poloxamer 407 Hydrogel as a Theragenerative Composite for Bone Cancer Treatment

Holmium-containing bioactive glasses can be applied in bone cancer treatment because the holmium content can be neutron activated, having suitable properties for brachytherapy applications, while the bioactive glass matrix can regenerate the bone alterations induced by the tumor. To facilitate the application of these glasses in clinical practice, we proposed a composite based on Poloxamer 407 thermoresponsive hydrogel, with suitable properties for applications as injectable systems. Therefore, in this work, we evaluated the influence of holmium-containing glass particles on the properties of Poloxamer 407 hydrogel (20 w/w.%), including self-assembly ability and biological properties. 58S bioactive glasses (58SiO2-33CaO-9P2O5) containing different Ho2O3 amounts (1.25, 2.5, 3.75, and 5 wt.%) were incorporated into the hydrogel. The formulations were characterized by scanning electron microscopy, differential scanning calorimetry, rheological tests, and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT cell viability against pre-osteoblastic and osteosarcoma cells. The results evidenced that neither the glass particles dispersed in the hydrogel nor the holmium content in the glasses significantly influenced the hydrogel self-assembly ability (Tmic ~13.8 °C and Tgel ~20 °C). Although, the glass particles considerably diminished the hydrogel viscosity in one order of magnitude at body temperature (37 °C). The cytotoxicity results evidenced that the formulations selectively favored pre-osteoblastic cell proliferation and osteosarcoma cell death. In conclusion, the formulation containing glass with the highest fraction of holmium content (5 wt.%) had the best biological results outcomes aiming its application as theragenerative materials for bone cancer treatment.

Rheological Properties Study of Oral Hydrogels Containing Phenobarbital for a Potiential Pediatric Use

This present study is a continuation of our work entitled “pH-thermosensitive oral chitosan-based hydrogels containing phenobarbital for a potential pediatric use”. The results of that previous study have shown their potential use in newborns in particular premature newborns while the oral form containing phenobarbital is a tablet and is unsuitable for newborns. Thus, in order to have a suitable device for the administration of hydrogels oral formulations to newborns, we have done rheology studies to complement our work. For this we have studied the variation of the viscosity of hydrogels containing phenobarbital as a function of shear rate and time. Phenobarbital is an active drug used in neonatal treatment of epilepsy. The viscosity measurements of hydrogels are carried out using a Fungilab V'PAD Rotational Viscometer (100–240V/50–60Hz) Type 'R series then ANOVA test was used to analysis the results. The results showed that the hydrogels had a non-Newtonian behavior with shear-thinning and thixotropic type which depends on the chitosan concentration, the storage temperature hydrogels, the presence of Eudragit E100 and the final solution’s pH. Rheological properties study have shown that a syringe-type device would be suitable for oral administration of hydrogels formulations to neonates.

Antibacterial polysaccharide-based hydrogel dressing containing plant essential oil for burn wound healing.

BackgroundPolysaccharide-based hydrogels have been developed for many years to treat burn wounds. Essential oils extracted from aromatic plants generally exhibit superior biological activity, especially antibacterial properties. Studies have shown that antibacterial hydrogels mixed with essential oils have great potential for burn wound healing. This study aimed to develop an antibacterial polysaccharide-based hydrogel with essential oil for burn skin repair.MethodsEucalyptus essential oil (EEO), ginger essential oil (GEO) and cumin essential oil (CEO) were employed for the preparation of effective antibacterial hydrogels physically crosslinked by carboxymethyl chitosan (CMC) and carbomer 940 (CBM). Composite hydrogels were prepared and characterized using antimicrobial activity studies, Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, gas chromatography-mass spectrometery, rheological analysis, viscosity, swelling, water loss rate and water vapor transmission rate studies. In addition, the biocompatibility of hydrogels was evaluated in vivo by cytotoxicity and cell migration assays and the burn healing ability of hydrogels was tested in vivo using burn-induced wounds in mice.ResultsThe different essential oils exhibited different mixing abilities with the hydrogel matrix (CMC and CBM), which caused varying levels of reduction in essential oil hydrogel viscosity, swelling and water vapor transmission. Among the developed hydrogels, the CBM/CMC/EEO hydrogel exhibited optimal antibacterial activities of 46.26 ± 2.22% and 63.05 ± 0.99% against Staphylococcus aureus and Escherichia coli, respectively, along with cell viability (>92.37%) and migration activity. Furthermore, the CBM/CMC/EEO hydrogel accelerated wound healing in mouse burn models by promoting the recovery of dermis and epidermis as observed using a hematoxylin–eosin and Masson’s trichrome staining assay. The findings from an enzyme-linked immunosorbent assay demonstrated that the CBM/CMC/EEO hydrogel could repair wounds through interleukin-6 and tumor necrosis factor-α downregulation and transforming growth factor-β, vascular endothelial growth factor (VEGF) and epidermal growth factor upregulation.ConclusionsThis study successfully prepared a porous CBM/CMC/EEO hydrogel with high antibacterial activity, favorable swelling, optimal rheological properties, superior water retention and water vapor transmission performance and a significant effect on skin repair in vitro and in vivo. The results indicate that the CBM/CMC/EEO hydrogel has the potential for use as a promising burn dressing material for skin burn repair.

RETRACTED ARTICLE: Osteoblastic differentiation of stem cells induced by graphene oxide-hydroxyapatite-alginate hydrogel composites and construction of tissue-engineered bone

This study aimed to investigate the effect of graphene oxide (GO)-hydroxyapatite (HA)-sodium alginate (SA) composite application in the field of bone tissue engineering. Four scaffold groups were established (SA-HA, SA-HA-0.8%GO, SA-HA-1.0%GO and SA-HA-1.2%GO) and mixed with bone marrow mesenchymal stem cells (BMSCs). Hydrogel viscosity was measured at room temperature, and after freeze-drying and Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) to detect substance crystallinity, the printability of each hydrogel type was measured with a printing grid. Scanning electron microscopy (SEM) was used to observe the internal microstructure of the scaffolds and to evaluate the growth and proliferation of cells on the scaffold. A hollow cylinder was printed to compare the forming effect of the hydrogel bioinks, and cell-hydrogel composites were implanted under the skin of nude mice to observe the effect of the hydrogels on osteogenesis in vivo. Increased GO concentrations led to reduced scaffold degradation rates, increased viscosity, increased printability, increased mechanical properties, increased scaffold porosity and increased cell proliferation rates. In vivo experiments showed that hematoxylin and eosin (HE) staining, Alizarin red staining, alkaline phosphatase staining and collagen type I immunohistochemical staining increased as the implantation time increased. These results demonstrate that GO composites have high printability as bioinks and can be used for bioprinting of bone by altering the ratio of the different components.

Injectable conductive hydrogel restores conduction through ablated myocardium.

Therapies for substrate-related arrhythmias include ablation or drugs targeted at altering conductive properties or disruption of slow zones in heterogeneous myocardium. Conductive compounds such as carbon nanotubes may provide a novel personalizable therapy for arrhythmia treatment by allowing tissue homogenization. A nanocellulose carbon nanotube-conductive hydrogel was developed to have conduction properties similar to normal myocardium. Ex vivo perfused canine hearts were studied. Electroanatomic activation mapping of the epicardial surface was performed at baseline, after radiofrequency ablation, and after uniform needle injections of the conductive hydrogel through the injured tissue. Gross histology was used to assess distribution of conductive hydrogel in the tissue. The conductive hydrogel viscosity was optimized to decrease with increasing shear rate to allow expression through a syringe. The direct current conductivity under aqueous conduction was 4.3 × 10-1 S/cm. In four canine hearts, when compared with the homogeneous baseline conduction, isochronal maps demonstrated sequential myocardial activation with a shift in direction of activation to surround the edges of the ablated region. After injection of the conductive hydrogel, isochrones demonstrated conduction through the ablated tissue with activation restored through the ablated tissue. Gross specimen examination demonstrated retention of the hydrogel within the tissue. This proof-of-concept study demonstrates that conductive hydrogel can be injected into acutely disrupted myocardium to restore conduction. Future experiments should focus on evaluating long-term retention and biocompatibility of the hydrogel through in vivo experimentation.

Effectiveness of viscous hydrogel in extinguishing burning solid substances

Introduction. When extinguishing burning solids, the use of water due to its high consumption and low insulating capacity of water films is ineffective. As a result of using viscous hydrogels as a fire extinguishing liquid, its consumption is reduced and a hydrogel film is formed on the burning surface, which has a greater thickness and better insulating ability compared to water. Aims and purposes. The aim of this study was to compare the effectiveness of using water and viscous hydrogels as a fire extinguishing liquid in the extinguishing of solid substances. The following tasks were solved: assessment of the impact of the concentration of gelling additives on the viscosity and evaporation of hydrogels; determination of the effect of viscosity of the fire extinguishing liquid film thickness and flow rate of liquid flowing from a vertical wall; a quantitative comparison of the effectiveness of fire suppression water, and various hydrogels according to their flow rate and film thickness. Methods. The influence of the concentration of gel-forming additives on the viscosity and evaporation of hydrogels was analyzed. An expression is obtained for the viscosity of the “Firesorb” hydrogel depending on the concentration of the polymer additive. The dependences of the evaporated mass of the hydrogel “Firesorb” from time to time at different concentrations of polymer additives. Evaluate the effectiveness of the use of hydrogels in their consumption and the thickness of the hydrogel films. The dependence of the film thickness of the extinguishing liquid flowing from the vertical wall on its viscosity and density is obtained. The coefficient of efficiency of hydrogel use is proposed, which characterizes the efficiency of hydrogel by its consumption and the insulating ability of the hydrogel film by its thickness. The efficiency of using hydrogels of different viscosities in comparison with water is calculated. Results and discussion. By changing the concentration of the gel-forming additive, you can vary the viscosity and evaporation of the hydrogel. The higher the viscosity of the hydrogel flowing from the vertical wall, the thicker the hydrogel film and less its consumption. Compared with water, the efficiency of using hydrogels is 2…4 times higher. Conclusions. The results obtained during the study indicate that the use of viscous hydrogels is effective in extinguishing burning solids.

Study on intelligent deformation characteristics of temperature‐driven hydrogel actuators prepared via molding and 3D printing

The poly‐N‐isopropylacrylamide intelligent hydrogel actuators with high mechanical strength and efficient temperature responses were successfully prepared via molding and three‐dimensional (3D) printing. Addition of nanofibrillated cellulose (NFC) effectively improved the crosslinking density and viscosity of hydrogels, enhancing the mechanical strength and 3D printable property. Based on sufficient polymerization on interface, bilayer hydrogel actuator prepared via molding exhibited efficient bending/unbending deformations. Bending degree in poikilothermy temperature ranging from 25°C to 55°C was higher than that in constant temperature of 55°C. Inspired by the rheology regulation of NFC, 3D printing intelligent hydrogel actuators with NFC content of 10 mg/mL were polymerized efficiently by ultraviolet irradiation. Self‐driven deformation characteristics of 3D printed intelligent hydrogels actuators were regulated via printing parameters including angle, width and length ratio and filling rate of the layered network structure model. The prepared hydrogel material system with molding and 3D printing ability provided material candidates for design and preparation of intelligent soft actuator and robot.

Anti-depressant effect of curcumin-loaded guanidine-chitosan thermo-sensitive hydrogel by nasal delivery

Curcumin, a polyphenol compound extracted from the roots of turmeric plants, possesses anti-depressant effect by regulating the levels of neuroendocrine immunological factors. The purpose of this study was to investigate the anti-depressant effect of curcumin through nasal delivery. The results of phase solubility, Fourier transform infrared spectra, Differential scanning calorimetry, X-ray powder diffractometry and 1H NMR spectra assays showed that curcumin/hydroxypropyl-β-cyclodextrin complex had been obtained. The viscosity of hydrogel increased rapidly at the temperature range of 29–30 °C through the test of rheological property of Guanidine-Chitosan thermo-sensitive hydrogel. And the hydrogel had good mucoadhesion properties. The cumulative release rate of curcumin was 55% in 10 h in vitro drug release test. Curcumin-loaded (14.6, 29.2, or 58.4 μg/kg) thermo-sensitive hydrogel could reduce the immobility time of mice in force swimming test and tail suspension test, while could not increase the independent behavioral activity of mice. In addition, curcumin-loaded (14.6, 29.2, or 58.4 μg/kg) thermo-sensitive hydrogel could increase the concentration of Norepinephrine, Dopamine, 5-Hydroxytryptamine and their metabolites in hippocampus and striatum. In conclusion, thermo-sensitive hydrogel delivery system can be seen as a promising formulation of curcumin for the treatment of depression through nasal delivery.

Applications of hydrogel composite multifunctional depots systems in rendering palliative care in otorhinolaryngology

Relevance. Throat cancer is the most widespread malignant tumor of a throat and makes about 3% of all malignant tumors of the person. Bleedings at throat cancer is the most difficult and dangerous complication posing direct threat to life of the oncological patient. An intervention is usually characterized by the expressed painful syndrome in a zone of surgical access for patients with surgical pathology of ENT organs. For that reason, using of gel polymeric dressing means is the most modern and effective. Analgesic action is noted in the area of a postoperative wound within the first 60 - 90 minutes after imposing of such bandage.
 Aim of research is to determine efficiency of multifunctional depot-system of the prolonged action on a gel basis of Kolegel-ADL of various degree of viscosity at a tamponade of a throat and trachea for elimination of a local hemorrhage.
 Materials and methods. Koletes-ADL dressing was used at treatment of 39 patients with malignant tumors of a throat. Patients arrived in the emergency order with bleedings from a throat, were on hospitalization in acute hospital No. 1, Voronezh. A morphological variety of malignant tumors of this localization took place. The control group has included 19 people with similar destructive and tumorous processes complicated by bleeding treatment of which was carried out by the standard technique.
 Results. As criteria of a convalescence considered the speed of reduction of the reactive phenomena in a wound and maturing of young granulations. Such characteristics like high viscosity of hydrogel dressing means, elastic consistency, entered into its structure antiseptics and local anesthetic allow to use it as tampon for a long period. One of essential advantages of use of Kolegel-ADL is creation a barrier impeding penetration of an infection into a skull cavity. The local anesthetic of Lidokin entered into structure of dressing means allows us stop a pain syndrome for a long time that reduces the need for parenteral introduction of anesthetics.
 Gauze-based dressings were used in the control group. There was injury to the wound surface when changing bandages, and the remains of gauze fibers in the wound led to inflammation.
 Conclusion. Multifunctional depot-system on a gel basis can be recommended as local antiedematous, haemostatic, antiseptic and anesthetic for local treatment of wound process in otorhinolaryngology, for therapy and prevention of purulent complications of wound surfaces of patients with oncological pathology of the throat complicated by bleeding.

Biocompatible, Injectable Anionic Hydrogels Based on Poly(Oligo Ethylene Glycol Monoacrylate‐co‐Acrylic Acid) for Protein Delivery

AbstractDevelopment of biocompatible hydrogels for sustained delivery of biological therapeutic agents is important for many regenerative medicine applications. In this study, a facile method is developed to synthesize injectable, anionic hydrogels based on poly(oligo ethylene glycol monoacrylate‐co‐acrylic acid) for protein controlled release. The synthesis of the copolymers is robust involving a single step of an aqueous free radical polymerization. These copolymers are then allowed to swell into the microporous injectable hydrogels. The covalent incorporation of the anionic group, acrylic acid, into the hydrogels increases the thermal stability and the viscosity of hydrogels due to the stronger intermolecular interactions in the copolymer network. These anionic groups also significantly enhance electrostatic interactions between the hydrogels and positively charged proteins, thus, rendering the hydrogels suitable for sustained release of the proteins under physiological conditions. An animal study shows these injectable hydrogels do not adversely affect wound healing. These findings warrant further investigation of these injectable hydrogels for their use in protein delivery for wound healing applications.

Development of multifunctional 3D printed bioscaffolds from polysaccharides and NiCu nanoparticles and their application

Abstract 3D printed bioscaffolds from polysaccharide materials hold a huge promise in tissue engineering applications, especially in regard to in vitro culturing of pancreatic cells, which require cell-ECM mimicking interactions in all spatial dimensions to remain viable for longer times. Material features, surface characteristics and the physical nature of scaffolds at multiple scales (e.g., macro-porosity, micro-topography) should be tailored to mimic crucial aspects of native or pathologically transformed tissues. With this in mind, we prepared hybrid hydrogel formulations from commonly used materials (alginate, carboxymethyl cellulose, nanofibrillated cellulose) and optimized them for 3D printing. With the intention to fine-tune their printability, rheological, mechanical, swelling, degradation and surface properties, variable concentrations of NiCu nanoparticles were incorporated into the mentioned hydrogels. We showed that NiCu nanoparticles might provide an effective tool for controlling hydrogel viscosity and scaffold swelling, degradation and surface properties. All scaffolds also promoted cell adhering, cell aggregation, cell migration and support long-term growth of pancreatic cells, which also displayed a physiologically more relevant morphology. This study lays the groundwork for development of novel 3D printed bioscaffolds with tailorable properties with the purpose to recapitulate characteristics of native tissues more closely.

The role of viscosity on skin penetration from cellulose ether‐based hydrogels

BackgroundThe rheological properties of dermal drug delivery systems are of importance when designing new formulations. Viscosity not only affects features such as spreadability and skin feel, but may also affect the skin penetration of incorporated actives. Data on the latter aspect are controversial. Our objective was to elucidate the relation between viscosity and drug delivery performance of different model hydrogels assuming that enhanced microviscosity might delay drug release and penetration.Materials and MethodsHydrogels covering a broad viscosity range were prepared by adding either HPMC or HEC as gelling agents in different concentrations. To investigate the ability of the gels to deliver a model drug into the skin, sulphadiazine sodium was incorporated and its in vitro skin penetration was monitored using tape stripping/HPLC analysis and non‐invasive confocal Raman spectroscopy.ResultsThe trends observed with the two different experimental setups were comparable. Drug penetration depths decreased slightly with increasing viscosity, suggesting slower drug release due to the increasingly dense gel networks. However, the total penetrated drug amounts were independent of the exact formulation viscosity.ConclusionDrug penetration was largely unaffected by hydrogel viscosity. Moderately enhanced viscosity is advisable when designing cellulose ether hydrogels to allow for convenient application.

Thermosensitive supramolecular and colloidal hydrogels via self-assembly modulated by hydrophobized cellulose nanocrystals

Utilization of reversible non-covalent interactions is a versatile design strategy for the development of stimuli responsive soft materials. In this study, hydrophobic interactions were harnessed to assemble water-soluble macromolecules and nanoparticles into a transient hybrid network forming thermosensitive hydrogels with tunable rheological properties. Hybrid hydrogels were built of biopolymer derived components: cellulose nanocrystals (CNCs), nanoparticles of high aspect ratio, and hydroxypropyl methylcellulose (HPMC). To enable polymer/CNC assembly via hydrophobic interactions, the surface of highly hydrophilic CNCs was modified by binding octyl moieties (octyl-CNCs). The amphiphilicity of octyl-CNCs was confirmed by surface tension measurements. The molecular and particulate amphiphiles assemble into hybrid networks, which result in stiffer and stronger hydrogels compared to HPMC hydrogels and hydrogels reinforced with hydrophilic CNCs. Hybrid hydrogels retain the ability of HPMC hydrogels to flow under applied shear stress. However, significantly higher viscosity was achieved for HPMC/octyl-CNCs compared with HPMC/CNCs hydrogels. The inherent thermal response of rheological properties of HPMC hydrogels was further amplified in combination with octyl-CNCs due to temperature-induced polymer/nanoparticle association via hydrophobic interactions. Saturation transfer difference NMR spectroscopy demonstrated the growth of network-bound water with an increase in temperature, which correlates with the increase of stiffness and viscosity of hydrogels upon heating. Rheological properties of these hybrid hydrogels are defined by the content of the soluble polymer and the CNCs, and it is shown that they can be finely adjusted for a required application.Graphical abstract

Enhanced photo/chemo combination efficiency against bladder tumor by encapsulation of DOX and ZnPC into in situ-formed thermosensitive polymer hydrogel.

BackgroundChemotherapy after transurethral resection is commonly recommended for bladder cancer. However, studies have shown that chemotherapy solely can hardly decrease progression rates of bladder cancer. The combination of chemotherapeutic agents with photo-dynamic therapy (PDT), a new promising localized therapy, may become a workable strategy for combating bladder cancer. This study reports the combination of doxorubicin (DOX)-based chemotherapy and zinc phthalocyanine (ZnPC)-based PDT using in situ-formed thermal-responsive copolymer hydrogel.Materials and methodsThe copolymer was synthesized by polymerization of 3-caprolactone, 1,4,8-trioxa[4.6]spiro-9-undecanone and poly(ethylene glycol) and was abbreviated as PCL-PTSUO-PEG. The thermal-responsive nanoparticles (TNPs) were prepared by the nanoprecipitation technology. The thermal-responsive hydrogel was formed after 37°C heating of TNP solution. The size, morphology and dynamic viscosity of hydrogel were detected. The in vitro drug release profile of TNP/DOX/ZnPC was performed. Cell uptake, cell inhibition and ROS generation of TNP/DOX/ZnPC were studied in 5637 cells. The in vivo antitumor activity of TNP/DOX/ZnPC was evaluated in nude mice bearing 5637 cells xenograft.ResultsTNP/DOX and TNP/ZnPC had an average diameter of 102 and 108 nm, respectively. After being heated at 37°C for 5 minutes, TNP/DOX and TNP/ZnPC solution turned uniform light red and dark green hydrogel. ZnPC encapsulation designed by TNP could significantly improve its aqueous solubility to 1.9 mg/mL. Cell inhibition showed that the best cell inhibition was found, with cell viability of 18.5%, when the weight ratio of DOX and ZnPC encapsulated in the TNP reached about 1:5. TNP/DOX/ZnPC generated relative high level of ROS with 4.8-fold of free ZnPC and 1.6-fold of TNP/ZnPC. TNP/DOX/ZnPC showed only 8-fold of relative tumor growth without obvious toxicity to the mice.ConclusionThermosensitive thermal-responsive hydrogel reported in this contribution are promising in situ-formed matrix for DOX- and ZnPC-based photo/chemo combination treatment for bladder cancer therapy.

Gelatin-Methacryloyl (GelMA) Hydrogels with Defined Degree of Functionalization as a Versatile Toolkit for 3D Cell Culture and Extrusion Bioprinting.

Gelatin-methacryloyl (GelMA) is a semi-synthetic hydrogel which consists of gelatin derivatized with methacrylamide and methacrylate groups. These hydrogels provide cells with an optimal biological environment (e.g., RGD motifs for adhesion) and can be quickly photo-crosslinked, which provides shape fidelity and stability at physiological temperature. In the present work, we demonstrated how GelMA hydrogels can be synthesized with a specific degree of functionalization (DoF) and adjusted to the intended application as a three-dimensional (3D) cell culture platform. The focus of this work lays on producing hydrogel scaffolds which provide a cell promoting microenvironment for human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) and are conductive to their adhesion, spreading, and proliferation. The control of mechanical GelMA properties by variation of concentration, DoF, and ultraviolet (UV) polymerization conditions is described. Moreover, hAD-MSC cell viability and morphology in GelMA of different stiffness was evaluated and compared. Polymerized hydrogels with and without cells could be digested in order to release encapsulated cells without loss of viability. We also demonstrated how hydrogel viscosity can be increased by the use of biocompatible additives, in order to enable the extrusion bioprinting of these materials. Taken together, we demonstrated how GelMA hydrogels can be used as a versatile tool for 3D cell cultivation.

Abstract 5018: Bioprinted (3D) co-cultured spheroids with NSCLC PDX cells and cancer associated fibroblasts (CAFs) using alginate/gelatin hydrogel

Abstract 3D bioprinting which is a significant improvement over 2D models offers layer by layer positioning of various cells which can provide superior cell-matrix interactions in the tumor microenvironment in vitro. The objective of the present study was to develop a co-culture model using Non-small cell lung cancer (NSCLC) patient derived xenograft (PDX) cells and lung cancer associated fibroblasts (CAFs) in sodium alginate/ gelatin hydrogel using a 3D bioprinter. Various concentrations of sodium alginate/gelatin hydrogels (w/w) were prepared and rheological properties were evaluated. PDX cells (EGFR T790M, obtained from Dr. Rishi's Laboratory, Wayne State University) and CAFs (AA0022, obtained from Dr. Noyes Laboratory, Moffit Cancer Center) were mixed with the hydrogel and printed usingINKREDIBLE bioprinter (Cellink, Sweden). A two layered cube was designed in Slic3r software, converted to g-code file and printed through a 22G needle. Printed scaffolds were cross linked by Crosslinking Agent (Cellink, Sweden) for 5 minutes, washed with HBSS and maintained with media at 37°C and 5% CO2. Spheroid formation was observed using an inverted microscope (Olympus IX70). Live/Dead and NucBlue/ActinGreen staining was performed to determine cell viability and spheroid formation. Immuno-fluorescence staining was performed for E-cadherin, α-SMA and vimentin to study cellular crosstalk within the spheroid. Printable hydrogels were prepared by adding 3.25% sodium alginate to 4% gelatin which was found to be the most optimal mixture. Decrease in storage modulus (G') from 995.29± 30.69 Pa to 12.16± 8.83 Pa and loss modulus (G”) from 314.10± 17.54 Pa to 22.22± 12.69 Pa was observed from 18°C to 37°C when using a temperature sweep test. At lowest shear rate (1s-1), the viscosity of the hydrogel was 2.75± 0.37 Pa.s and at 100s-1 the viscosity was 0.50± 0.12 Pa.s. Decrease in hydrogel viscosity with increasing shear rate confirmed shear thinning. The height, width and length of the printed scaffolds were found as 1.45± 0.06 mm, 9.56± 0.15 mm and10.67± 0.13 mm respectively. Formation of spheroids was observed after 4 days and after 15 days, 59.88± 14.81% small (0-400µm2), 15.43± 4.86% medium (401-1000 µm2) and 24.67± 10.14% large size spheroids (1001 µm2-above) were observed which indicated proliferation of individual cells within the scaffolds. LIVE/ DEAD assay showed approximately 82% cells were viable in the printed scaffold. Up-regulation of vimentin and α-SMA and concomitant loss of E-cadherin was observed in the printed co-cultures indicating cross talk between the two cells. This study demonstrates the preparation and characterization of NSCLC lung PDX and CAF co-culture spheroids in 3D bio-printed sodium alginate/ gelatin scaffold. This model can be further used for high throughput drug screening platform. Citation Format: Arindam Mondal, Aragaw Gebeyehu, Ramakrishnan Subramanian, Arun Rishi, Mandip Singh. Bioprinted (3D) co-cultured spheroids with NSCLC PDX cells and cancer associated fibroblasts (CAFs) using alginate/gelatin hydrogel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5018.

Control of cell morphology and differentiation by substrates with independently tunable elasticity and viscous dissipation

The mechanical properties of extracellular matrices can control the function of cells. Studies of cellular responses to biomimetic soft materials have been largely restricted to hydrogels and elastomers that have stiffness values independent of time and extent of deformation, so the substrate stiffness can be unambiguously related to its effect on cells. Real tissues, however, often have loss moduli that are 10 to 20% of their elastic moduli and behave as viscoelastic solids. The response of cells to a time-dependent viscous loss is largely uncharacterized because appropriate viscoelastic materials are lacking for quantitative studies. Here we report the synthesis of soft viscoelastic solids in which the elastic and viscous moduli can be independently tuned to produce gels with viscoelastic properties that closely resemble those of soft tissues. Systematic alteration of the hydrogel viscosity demonstrates the time dependence of cellular mechanosensing and the influence of viscous dissipation on cell phenotype.

Nanofibrillar cellulose-alginate hydrogel coated surgical sutures as cell-carrier systems.

Hydrogel nanomaterials, especially those that are of non-human and non-animal origins, have great potential in biomedical and pharmaceutical sciences due to their versatility and inherent soft-tissue like properties. With the ability to simulate native tissue function, hydrogels are potentially well suited for cellular therapy applications. In this study, we have fabricated nanofibrillar cellulose-alginate (NFCA) suture coatings as biomedical devices to help overcome some of the limitations related to cellular therapy, such as low cell survivability and distribution out of target tissue. The addition of sodium alginate 8% (w/v) increased the NFCA hydrogel viscosity, storage and loss moduli by slightly under one order of magnitude, thus contributing significantly to coating strength. Confocal microscopy showed nearly 100% cell viability throughout the 2-week incubation period within and on the surface of the coating. Additionally, typical morphologies in the dual cell culture of spheroid forming HepG2 and monolayer type SK-HEP-1 were observed. Twelve out of 14 NFCA coated surgical sutures remained intact during the suturing operation with various mice and rat tissue; however, partial peeling off was observed in 2 of the coated sutures. We conclude that NFCA suture coatings could perform as cell-carrier systems for cellular based therapy and post-surgical treatment.

Insight into halloysite nanotubes-loaded gellan gum hydrogels for soft tissue engineering applications

A tri-component hydrogel, based on gellan gum (GG), glycerol (Gly) and halloysite nanotubes (HNT), is proposed in this work for soft tissue engineering applications. The FDA-approved GG polysaccharide has been recently exploited as biomaterial because its biomimetic features. Gly is added as molecular spacer to improve hydrogel viscosity and mechanical properties. HNT incorporation within the hydrogel offers the versatility to improve the GG-Gly biocompatibility with potential incorporation of target biomolecules. In this work, hydrogels with different composition ratios are physically crosslinked for tuning physico-mechanical properties. An accurate physico-chemical characterization is reported. HNT addition leads to a water uptake decrease of 30–35% and tuneable mechanical properties with a compressive Young’s modulus ranging between 20 and 75kPa. Finally, in vitro study with human fibroblasts on GG-Gly hydrogels loaded with 25% HNT offered the higher metabolic activities and cell survival up to 7days of incubation.

Formulation of Novel Glycerin Nanoparticles for Enhancement the Solubility of Loratadine; Application to Transdermal Hydrogel Delivery System

Owing to its slightly aqueous solubility, loratadine (LOR) is used in high doses in different marketed formulations to achieve its desirable bioavailability. The aim of this work is to formulate novel LOR-glycerin nanoparticles (LOR-GNPs) to increase LOR bioavailability. LOR-GNPs were prepared by a precipitation method and then evaluated for such size and morphology using dynamic scattering spectroscopy (DLS) and scanning electron microscopy (SEM), as well as the percentage entrapment efficiency (EE%) of free LOR from GNPs formulations was performed using titration method. Furthermore, the GNPs were formulated in hydrogel. The hydrogel viscosity, spreadability, homogeneity and abdominal rat skin permeation were studied and optimized DLS indicated a successful coating of LOR with glycerin surface that recorded an average size of 334 ± 30 nm with uniform particle size, while SEM showed LOR-NPs in different shapes. The EE% free LOR was found to be satisfactory with a mean content of 98.1 ± 0.3 and a relative standard deviation below 2.0% indicates the reproducibility of the LOR release. LOR-GNPs were formulated as a hydrogel to check their suitability for a dosage form usage. The hydrogel showed accepted viscosity, spreadability, and homogeneity. The results proved that the GNPs penetrated abdominal rat skin. The obtained results showed that LOR-GNPs are considered a new addition for improvement of LOR solubility when applied as a hydrogel. The developed method could be used for different insoluble candidates.