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by Keyword: Hydrogels


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Olate-Moya, F., Arens, L., Wilhelm, M., Mateos-Timoneda, M. A., Engel, E., Palza, H., (2020). Chondroinductive alginate-based hydrogels having graphene oxide for 3D printed scaffold fabrication ACS Applied Materials and Interfaces 12, (4), 4343-4357

Scaffolds based on bioconjugated hydrogels are attractive for tissue engineering because they can partly mimic human tissue characteristics. For example, they can further increase their bioactivity with cells. However, most of the hydrogels present problems related to their processability, consequently limiting their use in 3D printing to produce tailor-made scaffolds. The goal of this work is to develop bioconjugated hydrogel nanocomposite inks for 3D printed scaffold fabrication through a micro-extrusion process having improved both biocompatibility and processability. The hydrogel is based on a photocrosslinkable alginate bioconjugated with both gelatin and chondroitin sulfate in order to mimic the cartilage extracellular matrix, while the nanofiller is based on graphene oxide to enhance the printability and cell proliferation. Our results show that the incorporation of graphene oxide into the hydrogel inks considerably improved the shape fidelity and resolution of 3D printed scaffolds because of a faster viscosity recovery post extrusion of the ink. Moreover, the nanocomposite inks produce anisotropic threads after the 3D printing process because of the templating of the graphene oxide liquid crystal. The in vitro proliferation assay of human adipose tissue-derived mesenchymal stem cells (hADMSCs) shows that bioconjugated scaffolds present higher cell proliferation than pure alginate, with the nanocomposites presenting the highest values at long times. Live/Dead assay otherwise displays full viability of hADMSCs adhered on the different scaffolds at day 7. Notably, the scaffolds produced with nanocomposite hydrogel inks were able to guide the cell proliferation following the direction of the 3D printed threads. In addition, the bioconjugated alginate hydrogel matrix induced chondrogenic differentiation without exogenous pro-chondrogenesis factors as concluded from immunostaining after 28 days of culture. This high cytocompatibility and chondroinductive effect toward hADMSCs, together with the improved printability and anisotropic structures, makes these nanocomposite hydrogel inks a promising candidate for cartilage tissue engineering based on 3D printing.

Keywords: 3D printing, Chondrogenesis, Graphene oxide, Hydrogels, Liquid crystals


Bertran, O., Saldías, C., Díaz, D. D., Alemán, C., (2020). Molecular dynamics simulations on self-healing behavior of ionene polymer-based nanostructured hydrogels Polymer 211, 123072

The microscopic mechanism accounting for the self-healing attribute of aromatic ionene-forming hydrogels derived from 1,4-diazabicyclo [2.2.2]octane (DABCO) and N,N’-(x-phenylene)dibenzamide (x = ortho-/meta-/para-) is unknown. Interestingly, the self-healing property of such DABCO-containing hydrogels is largely dependent on the polymer topology, the ortho ionene being the only self-healable without adding oppositely charged species. In this work, Molecular Dynamics (MD) simulations have been conducted to evaluate the influence of the topology on ionene···ionene and ionene··water interactions, as well as their effect on the self-healing behavior. For this purpose, destabilized and structurally damaged models were produced for ionene hydrogels with ortho, meta and para topologies and used as starting geometries for simulations. These models were allowed to evolve without any restriction during MD production runs and, subsequently, the temporal evolution of ionene···ionene and water···ionene interactions was examined. Analysis of the results indicated that the ortho-isomer rapidly forms unique interactions that are not detected for other two isomers. Thus, in addition to the interactions also identified for the meta-and para-ionenes, the ortho-isomer exhibits the formation of strong intermolecular three-centered (N–)H⋯O (=C)⋯H (–N) hydrogen bonds, intramolecular planar sandwich π-π stacking interactions and Cl−···N+ electrostatic interactions. Furthermore, the amount of intermolecular π-π stacking interactions and the strength of water···polymer interaction are also influenced by the topology, favoring the stabilization of the ortho-ionene reconstituted hydrogels. Overall, the arrangement of the functional groups in the ortho topology favors the formation of more types of ionene···ionene interactions, as well as stronger interactions, than in the meta and para topologies.

Keywords: DABCO, Econstituted hydrogels, Molecular dynamics, Polyelectrolyte hydrogels, Self-healing mechanism


Fuentes, E., Bohá, Fuentes-Caparrós, A. M., Schweins, R., Draper, E. R., Adams, D. J., Pujals, S., Albertazzi, L., (2020). PAINT-ing fluorenylmethoxycarbonyl (Fmoc)-diphenylalanine hydrogels Chemistry - A European Journal 26, (44), 9869-9873

Self-assembly of fluorenylmethoxycarbonyl-protected diphenylalanine (FmocFF) in water is widely known to produce hydrogels. Typically, confocal microscopy is used to visualize such hydrogels under wet conditions, that is, without freezing or drying. However, key aspects of hydrogels like fiber diameter, network morphology and mesh size are sub-diffraction limited features and cannot be visualized effectively using this approach. In this work, we show that it is possible to image FmocFF hydrogels by Points Accumulation for Imaging in Nanoscale Topography (PAINT) in native conditions and without direct gel labelling. We demonstrate that the fiber network can be visualized with improved resolution (≈50 nm) both in 2D and 3D. Quantitative information is extracted such as mesh size and fiber diameter. This method can complement the existing characterization tools for hydrogels and provide useful information supporting the design of new materials.

Keywords: FmocFF, Hydrogels, Mesh size, PAINT, Super-resolution


Maiti, B., Abramov, A., Franco, L., Puiggalí, J., Enshaei, H., Alemán, C., Díaz, D. D., (2020). Thermoresponsive shape-memory hydrogel actuators made by phototriggered click chemistry Advanced Functional Materials 30, (24), 2001683

This article describes the design and synthesis of a new series of hydrogel membranes composed of trialkyne derivatives of glycerol ethoxylate and bisphenol A diazide (BA-diazide) or diazide-terminated PEG600 monomer via a Cu(I)-catalyzed photoclick reaction. The water-swollen hydrogel membranes display thermoresponsive actuation and their lower critical solution temperature (LCST) values are determined by differential scanning calorimetry. Glycerol ethoxylate moiety serves as the thermoresponsive component and hydrophilic part, while the azide-based component acts as the hydrophobic comonomer and most likely provides a critical hydrophobic/hydrophilic balance contributing also to the significant mechanical strength of the membranes. These hydrogels exhibit a reversible shape-memory effect in response to temperature through a defined phase transition. The swelling and deswelling behavior of the membranes are systematically examined. Due to the click nature of the reaction, easy availability of azide and alkyne functional-monomers, and the polymer architecture, the glass transition temperature (Tg) is easily controlled through monomer design and crosslink density by varying the feed ratio of different monomers. The mechanical properties of the membranes are studied by universal tensile testing measurements. Moreover, the hydrogels show the ability to absorb a dye and release it in a controlled manner by applying heat below and above the LCST.

Keywords: Hydrogels, Membranes, Photoclick, Polymers, Shape-memory, Thermoresponsive


Lanzalaco, S., Turon, P., Weis, C., Mata, C., Planas, E., Alemán, C., Armelin, E., (2020). Toward the new generation of surgical meshes with 4D response: Soft, dynamic, and adaptable Advanced Functional Materials 30, (36), 2004145

Herein, a facile approach toward transforming a 2D polypropylene flexible mesh material into a 4D dynamic system is presented. The versatile platform, composed by a substrate of knitted fibers of isotactic polypropylene (iPP) mesh and a coating of thermosensitive poly(N‐isopropylacrylamide‐co‐N,N’‐methylene bis(acrylamide) (PNIPAAm‐co‐MBA) hydrogel, covalently bonded to the mesh surface, after cold‐plasma surface treatment and radical polymerization, is intended to undergo variations in its geometry via its reversible folding/unfolding behavior. The study is the first to trace the 3D movement of a flat surgical mesh, intended to repair hernia defects, under temperature and humidity control. An infrared thermographic camera and an optical microscope are used to evaluate the macroscopic and microscopic structure stimulus response. The presence of the PP substrate and the distribution of the gel surrounding the PP threads, affect both the PNIPAAM gel expansion/contraction as well as the time of folding/unfolding response. Furthermore, PP‐g‐PNIPAAm meshes show an increase in the bursting strength of ≈16% with respect to the uncoated mesh, offering a strongest and adaptable system for its future implantation in human body. The findings reported offer unprecedented application possibilities in the biomedical field.

Keywords: Dynamic devices, Polypropylene meshes, Surgical implants, Thermosensitive hydrogels


Otero, J., Navajas, D., Alcaraz, J., (2020). Characterization of the elastic properties of extracellular matrix models by atomic force microscopy Methods in Cell Biology (ed. Caballero, David, Kundu, Subhas C., Reis, Rui L.), Academic Press (Cambridge, USA) 156, 59-83

Tissue elasticity is a critical regulator of cell behavior in normal and diseased conditions like fibrosis and cancer. Since the extracellular matrix (ECM) is a major regulator of tissue elasticity and function, several ECM-based models have emerged in the last decades, including in vitro endogenous ECM, decellularized tissue ECM and ECM hydrogels. The development of such models has urged the need to quantify their elastic properties particularly at the nanometer scale, which is the relevant length scale for cell-ECM interactions. For this purpose, the versatility of atomic force microscopy (AFM) to quantify the nanomechanical properties of soft biomaterials like ECM models has emerged as a very suitable technique. In this chapter we provide a detailed protocol on how to assess the Young's elastic modulus of ECM models by AFM, discuss some of the critical issues, and provide troubleshooting guidelines as well as illustrative examples of AFM measurements, particularly in the context of cancer.

Keywords: 3D ECM hydrogels, Atomic force microscopy, Decellularized tissue, Elastic modulus, Endogenous ECM, Extracellular matrix


De Koker, Stefaan, Cui, Jiwei, Vanparijs, Nane, Albertazzi, Lorenzo, Grooten, Johan, Caruso, Frank, De Geest, Bruno G., (2016). Engineering polymer hydrogel nanoparticles for lymph node-targeted delivery Angewandte Chemie - International Edition 55, (4), 1334-1339

The induction of antigen-specific adaptive immunity exclusively occurs in lymphoid organs. As a consequence, the efficacy by which vaccines reach these tissues strongly affects the efficacy of the vaccine. Here, we report the design of polymer hydrogel nanoparticles that efficiently target multiple immune cell subsets in the draining lymph nodes. Nanoparticles are fabricated by infiltrating mesoporous silica particles (ca. 200 nm) with poly(methacrylic acid) followed by disulfide-based crosslinking and template removal. PEGylation of these nanoparticles does not affect their cellular association in vitro, but dramatically improves their lymphatic drainage in vivo. The functional relevance of these observations is further illustrated by the increased priming of antigen-specific T cells. Our findings highlight the potential of engineered hydrogel nanoparticles for the lymphatic delivery of antigens and immune-modulating compounds.

Keywords: Dendritic cells, Disulfides, Hydrogels, Nanoparticles, Vaccines


Yue, J. J., Morgenstern, R., Morgenstern, C., Lauryssen, C., (2011). Shape memory hydrogels - A novel material for treating age-related degenerative conditions of the Spine European Musculoskeletal Review , 6, (3), 184-188

Hydrogels are water-insoluble hydrophilic polymers used in a wide range of medical products such as, drug delivery, tissue replacement, heart surgery, gynaecology, ophthalmology, plastic surgery and orthopaedic surgery. These polymers exhibit low toxicity, reduced tissue adherence, and are highly biocompatible. A class of hydrogels, hydrolysed polyacrylonitriles, possess unique shape memory properties, which, when combined with biodurability, mechanical strength and viscoelasticity make them ideal for treating certain degenerative conditions of the spine. Animal and other in vitro studies have shown that the hydrogel is biocompatible and well tolerated by host tissues. This article focuses on two specific indications in spine surgery that demonstrate the potential of hydrogel-based technology to provide significant treatment advantages.

Keywords: Biocompatibility, Degenerative disc disease, Hydrolysed polyacrylonitrile, Minimally invasive surgery, Shape memory hydrogel, Spinal stenosis