Fast Gelling Research Articles

Fast gelling, high performance MXene hydrogels for wearable sensors

Hydrogel-based functional materials had attracted great attention in the fields of artificial intelligence, soft robotics, and motion monitoring. However, the gelation of hydrogels induced by free radical polymerization typically required heating, light exposure, and other conditions, limiting their practical applications and development in real-life scenarios. In this study, a simple and direct method was proposed to achieve rapid gelation at room temperature by incorporating reductive MXene sheets in conjunction with metal ions into the chitosan network and inducing the formation of a polyacrylamide network in an extremely short time (10 s). This resulted in a dual-network MXene-crosslinked conductive hydrogel composite that exhibited exceptional stretchability (1350 %), remarkably low dissipated energy (0.40 kJ m−3 at 100 % strain), high sensitivity (GF = 2.86 at 300–500 % strain), and strong adhesion to various substrate surfaces. The study demonstrated potential applications in the reliable detection of various motions, including repetitive fine movements and large-scale human body motions. This work provided a feasible platform for developing integrated wearable health-monitoring electronic systems.

Abstract P2133: Preservation & Vascularization Of Cardiac Extracellular Matrix After Acute Myocardial Infarction

Following myocardial infarction (MI), the upregulated matrix metalloproteinases (MMPs) especially MMP-2/9 lead to the degradation of cardiac extracellular matrix (ECM), leading to impaired cardiac function. Therefore, preservation of cardiac ECM by decreasing MMP-2/9 acitivity will increase cardiac function. Meanwhile, vascularization is critical for cardiac ECM as otherwise its structure and composition change over time. In this work, a non-toxic peptide CTTHWGFTLC (CTT) that specifically inhibits MMP-2/9, and a pro-angiogenic basic fibroblast growth factor (bFGF) were used to preserve and vascularize the cardiac ECM. A fast gelling, degradable, and reactive oxygen species (ROS)-scavenging hydrogel was developed to deliver CTT and bFGF to the infarcted hearts. We evaluated the efficacy of the delivery system in preserving and vascularizing cardiac ECM, and improving cardiac function. The combination of CTT and bFGF synergistically promoted tube formation of HUVECs compared to the treatment with CTT or bFGF (**p<0.01). Interestingly, both CTT and bFGF inhibited myofibroblast differentiation of cardiac fibroblasts. The combination of CTT and bFGF further significantly decreased the differentiation. After 28 days of implantation of the CTT/bFGF/Gel, the wall thickness was significantly increased compared to the CTT/Gel, bFGF/Gel, Gel only and MI. The released CTT and bFGF preserved cardiac ECM, decreased cardiac fibrosis, and stimulated angiogenesis in the infarcted area, leading to a significant increase of cardiac function.

Precipitation‐Based Silk Fibroin Fast Gelling, Highly Adhesive, and Magnetic Nanocomposite Hydrogel for Repair of Irregular Bone Defects

AbstractCritical‐sized bone defects, especially for irregular shapes, remain a significant challenge in orthopedics. Although various biomaterials are developed for bone regeneration, their application for repair of irregular bone defects is limited by the complicated preparation procedures involved, and their lack of shape‐adaptive capacity, physiological adhesion, and potent osteogenic bioactivity. In the present study, a simple strategy of precipitation by introducing tannic acid (TA) with abundant phenolic hydroxyl groups and Fe3O4 nanoparticles, as metal‐phenolic networks (MPN), is developed to easily prepare a fast gelling, shape‐adaptive, and highly adhesive regenerated silk fibroin (RSF)/TA/Fe3O4 hydrogel system that can respond to a static magnetic field (SMF). The RSF/TA/Fe3O4 hydrogel exhibits sufficient adhesion in biological microenvironments and good osteogenic effect in vitro and in vivo, under an external SMF, and thus, can be applied to repair critical‐sized bone defects. Moreover, bioinformatics analysis reveals that the synergistic mechanism of Fe3O4 NPs and SMF on osteogenic effects can be promotion of osteoblast differentiation via activation of the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)/extracellular signal‐regulated kinase (ERK) signaling pathway. This study provides a promising biomaterial with potential clinical application for the future treatment of (irregular) critical‐sized bone defects.

Mussel-inspired blue-light-activated cellulose-based adhesive hydrogel with fast gelation, rapid haemostasis and antibacterial property for wound healing

A fast gelation, rapid haemostasis and antibacterial property allyl cellulose/P(DOPMAm- co -MPTC) (AC/PDM) adhesive hydrogel for wound healing was fabricated by blue-light-activated double-network strategy. • The AC/PDM hydrogel was designed by blue-light-activated double-network strategy. • The hydrogel possessed strong tissue adhesive strength. • The hydrogel exhibited fast gelation and high antibacterial properties. • The hydrogel showed excellent haemostatic capability and wound healing performance. Uncontrollable bleeding and wound infection remain as the primary challenges for emergency surgical procedures, including deep and non-compressible bleeding in the clinic or on the battleground. To better control haemorrhaging immediately from irregularly shaped and non-compressible wounds, double-network adhesive hydrogels based on cellulose and 3,4-dihydroxyphenylalanine (DOPA)-cation copolymer were designed for wound healing. Due to the abundance of hydrogen bonding, π-π stacking, cation-π and electrostatic interactions in the double-network adhesives, the hydrogel with good biocompatibility presented tissue-like mechanical strength with Young’s modulus below 20 kPa. The catechol-cation cooperation effect enhances the wet adhesion of hydrogels to skin tissue surfaces. The blue-light-induced fast gelation networks provide rapid haemostasis ability of the hydrogels by sealing blood vessels. The quaternary ammonium cationic polymers have remarkable antibacterial properties and promote blood coagulation by erythrocyte and platelet aggregation. Furthermore, the hydrogel with 2.5% P(DOPMAm- co -MPTC) (AC/PDM 2.5 ) exhibited better tissue adhesion strength than commercially available glue, better haemostatic capability than the gauze based on the mouse-tail amputation model, and higher performance compared to Tegaderm™ in the rat full-thickness skin defect model. These adhesive hydrogels with fast gelling, rapid haemostasis, biocompatibility and antibacterial activity offer great promising applications in wound healing.

Particle and Gel Characterization of Irinotecan-Loaded Double-Reverse Thermosensitive Hydrogel

The irinotecan-loaded double-reverse thermosensitive hydrogel (DRTH) is a dispersed system of irinotecan-loaded solid lipid nanoparticles (SLN) in a thermosensitive hydrogel. To optimise the particle and gel properties of DRTHs for rectal administration of irinotecan, SLNs and DRTHs were prepared with tricaprin, triethanolamine, Tween 80, and Span 20. Among the SLNs tested, an SLN composed of 1 g irinotecan, 0.5 g lipid mixture, and 0.5 g combined surfactant gave the highest entrapment efficiency and smallest particle size. A DRTH composed of (poloxamer 407/poloxamer 188/combined surfactant/SLN dispersion/H2O (10/15/17/4/54%)) showed easy administration, fast gelling, and strong gel-forming in the body.

Modulating biodegradation and biocompatibility of in situ crosslinked hydrogel by the integration of alginate into N,O-carboxylmethyl chitosan – aldehyde hyaluronic acid network

This study aims to investigate the mutual effect of integrating alginate (Alg) into N,O-carboxymethyl chitosan (NOCC) – aldehyde hyaluronic acid (AHA) network regarding degradation behavior and biocompatibility of the hybrid hydrogel. The introduction of Alg not only generated the synergistic effect between electrostatic interaction and Schiff-base crosslinking, which was proved to significantly enhance the system stability and prolong degradation time, but also circumvented the limitation of bio-inert property of Alg-based composites. This approach is versatile and does not required extra effort to modify chemical compositions of the hydrogel components. Fourier Transform Infrared Spectroscopy (FT-IR) analysis was used to study the crosslinking mechanism of obtained fast gelling hybrid. The variation of volume ratios between three constituent components was found to modulate the gel-forming ability, biodegradation and biocompatibility of acquired hydrogel networks. Among investigated formulations, 6:4(1:1) NOCC-Alg-AHA sample possessed desired interconnected porous structure as shown by SEM technique, appropriate water uptake capacity, extended degradation time and excellent cell attachment and proliferation through in vitro studies, which is a promising injectable scaffold and/or encapsulating substrate for tissue engineering applications.

Fast gelling and non-swellable photopolymerized poly (vinyl alcohol) hydrogels with high strength

Despite their great potential in biomedical applications, the use of hydrogels has been severely limited by their swelling property and weak strength under physiological conditions. Herein, we developed nonswelling and high-strength hydrogels by a facile one-step thiol-acrylate photopolymerization of methacrylated poly (vinyl alcohol) and thiol-terminated poly (vinyl alcohol) for the first time. The hydrogels can gel rapidly within 7 s in this approach. By controlling crosslinking density and hydrophilic/hydrophobic balance of cross-linking hydrogel networks, the properties of hydrogels can be tunable and can even exhibit an excellent nonswelling behaviour under physiological conditions. Notably, the outstanding mechanical property with a compressive strength of 7.0 MPa at ~95% strain as well as no damage through compressive stress–strain tests in the allowable scope of tensile tester can also be achieved. Moreover, the hydrogel is non-toxic to L929 cells, which is favorable for promising biomedical applications as implants and tissue engineering scaffolds.

Thermosensitive, fast gelling, photoluminescent, highly flexible, and degradable hydrogels for stem cell delivery

Stem cell therapy is a promising approach to regenerate ischemic cardiovascular tissues yet experiences low efficacy. One of the major causes is inferior cell retention in tissues. Injectable cell carriers that can quickly solidify upon injection into tissues so as to immediately increase viscosity have potential to largely improve cell retention. A family of injectable, fast gelling, and thermosensitive hydrogels were developed for delivering stem cells into heart and skeletal muscle tissues. The hydrogels were also photoluminescent with low photobleaching, allowing for non-invasively tracking hydrogel biodistribution and retention by fluorescent imaging. The hydrogels were polymerized by N-isopropylacrylamide (NIPAAm), 2-hydroxyethyl methacrylate (HEMA), 1-vinyl-2-pyrrolidinone (VP), and acrylate-oligolactide (AOLA), followed by conjugation with hypericin (HYP). The hydrogel solutions had thermal transition temperatures around room temperature, and were readily injectable at 4 °C. The solutions were able to quickly solidify within 7 s at 37 °C. The formed gels were highly flexible possessing similar moduli as the heart and skeletal muscle tissues. In vitro, hydrogel fluorescence intensity decreased proportionally to weight loss. After being injected into thigh muscles, the hydrogel can be detected by an in vivo imaging system for 4 weeks. The hydrogels showed excellent biocompatibility in vitro and in vivo, and can stimulate mesenchymal stem cell (MSC) proliferation and paracrine effects. The fast gelling hydrogel remarkably increased MSC retention in thigh muscles compared to slow gelling collagen, and non-gelling PBS. These hydrogels have potential to efficiently deliver stem cells into tissues. Hydrogel degradation can be non-invasively and real-time tracked. Statement of SignificanceLow cell retention in tissues represents one of the major causes for limited therapeutic efficacy in stem cell therapy. A family of injectable, fast gelling, and thermosensitive hydrogels that can quickly solidify upon injection into tissues were developed to improve cell retention. The hydrogels were also photoluminescent, allowing for non-invasively and real-time tracking hydrogel biodistribution and retention by fluorescent imaging.

Control of viscous instability by variation of injection rate in a fluid with time-dependent rheology

Using variational calculus, we investigate the time-dependent injection rate that minimises the growth of the Saffman–Taylor instability when a finite volume of fluid is injected in a finite time, $t_{f}$, into a Hele-Shaw cell. We first consider a planar interface, and show that, with a constant viscosity ratio, the constant injection rate is optimal. When the viscosity of the displacing fluid, $\unicode[STIX]{x1D707}_{1}(t)$, gradually increases over time, as may occur with a slowly gelling polymer solution, the optimal injection rate, $U^{\ast }(t)$, involves a gradual increase in the flow rate with time. This leads to a smaller initial value of flow rate than the constant injection rate, finishing with a larger value. Such optimisation can lead to a substantial suppression of the instability as compared to the constant injection case if the characteristic gelling time is comparable to $t_{f}$. In contrast, for either relatively slow or fast gelling, there is much less benefit in selecting the optimal injection rate, $U^{\ast }(t)$, as compared to the constant injection rate. In the case of a constant injection rate from a point source, $Q$, then with a constant viscosity ratio the fastest-growing perturbation on the radially spreading front involves axisymmetric modes whose wavenumber increases with time. Approximating the discrete azimuthal modes by a continuous distribution, we find the injection rate that minimises growth, $Q^{\ast }(t)$. We find that there is a critical time for injection, $t_{f}^{\dagger }$, such that if $t_{f}>t_{f}^{\dagger }$ then $Q^{\ast }(t)$ can be chosen so that the interface is always stable. This critical time emerges from the case with an injection rate given by $Q^{\ast }\sim t^{-1/3}$. As the total injection time is reduced to values $t_{f}<t_{f}^{\dagger }$, the system becomes progressively more unstable, and the optimal injection rate for an idealised continuous distribution of azimuthal modes asymptotes to a flow rate that increases linearly with time. As for the one-dimensional case, if the viscosity of the injection fluid gradually increases over time, then the optimal injection rate has a smaller initial value but gradually increases to larger values than for the analogous constant viscosity problem. If the displacing fluid features shear-thinning rheology, then the optimal injection rate involves a smaller flow rate at early times, although not as large a reduction as in the Newtonian case, and a larger flow rate at late times, although not as large an increase as in the Newtonian case.

Role of sonication pre-treatment and cation valence in the sol-gel transition of nano-cellulose suspensions

Sol-gel transition of carboxylated cellulose nanocrystals has been investigated using rheology, SAXS, NMR and optical spectroscopies to unveil the distinctive roles of ultrasound treatments and addition of various cations. Besides cellulose fiber fragmentation, sonication treatment induces fast gelling of the solution. The gelation is independent of the addition of cations, while the final rheological properties are highly influenced by the type, concentration and sequence of the operations since the cations must be added prior to sonication to produce stiff gels. The gel elastic modulus was found to increase proportionally to the ionic charge rather than the cationic size. In cases where ions were added after sonication, SAXS analysis of the Na+ hydrogel and Ca2+ hydrogel indicated the presence of structurally ordered domains in which water is confined, and 1H-NMR investigation showed the dynamics of water exchange within the hydrogels. Conversely, separated phases containing essentially free water were characteristic of the hydrogels obtained by sonication after Ca2+ addition, confirming that this ion induces irreversible fiber aggregation. The rheological properties of the hydrogels depend on the duration of the ultrasound treatments, enabling the design of programmed materials with tailored energy dissipation response.

Ocular Disposition of ∆8-Tetrahydrocannabinol from Various Topical Ophthalmic Formulations.

The purposes of this project are to enhance the trans-membrane penetration of Δ8-Tetrahydrocannabinol (Δ8-THC) and to study the effect of various lipid based systems in delivering the compound, non-invasively, to anterior and posterior ocular chambers. Solid lipid nanoparticles (SLNs), fast gelling films were manufactured using high pressure homogenization and melt cast techniques, respectively. The formulations were characterized for drug content, entrapment efficiency, particle size and subsequently evaluated in vitro for trans-corneal permeation. In vivo, the drug disposition was tested via topical administration in albino rabbits. The eye globes were enucleated at the end of experiment and tissues were analyzed for drug content. All formulations showed favorable physicochemical characteristics in terms of particle size, entrapment efficiency, and drug content. In vitro, the formulations exhibited a transcorneal flux that depended on the formulation's drug load. An increase in drug load from 0.1 to 0.75% resulted in 12- to16-folds increase in permeation. In vivo, the film was able to deliver THC to all the tissues with high accumulations in cornea and sclera. The SLNs showed a greater ability in delivering THC to all the tissues, at a significantly lower drug load, due to their colloidal size range, which in turn enhanced corneal epithelial membrane penetration. The topical formulations evaluated in the present study were able to successfully deliver Δ8-THC in therapeutically meaningful concentrations (EC50 values for CB1: 6nM and CB2: 0.4nM) to all ocular tissues except the vitreous humor, with pronounced tissue penetration achieved using SLNs as a Δ8-THC delivery vehicle.

Cell-laden hydrogel/titanium microhybrids: Site-specific cell delivery to metallic implants for improved integration

Porous titanium implants are widely used in dental, orthopaedic and otorhinolaryngology fields to improve implant integration to host tissue. A possible step further to improve the integration with the host is the incorporation of autologous cells in porous titanium structures via cell-laden hydrogels. Fast gelling hydrogels have advantageous properties for in situ applications such as localisation of specific cells and growth factors at a target area without dispersion. The ability to control the cell types in different regions of an implant is important in applications where the target tissue (i) has structural heterogeneity (multiple cell types with a defined spatial configuration with respect to each other); (ii) has physical property gradients essential for its function (such as in the case of osteochondral tissue transition). Due to their near immediate gelation, such gels can also be used for site-specific modification of porous titanium structures, particularly for implants which would face different tissues at different locations. Herein, we describe a step by step design of a model system: the model cell-laden gel-containing porous titanium implants in the form of titanium microbead/hydrogel (maleimide-dextran or maleimide-PVA based) microhybrids. These systems enable the determination of the effect of titanium presence on gel properties and encapsulated cell behaviour as a miniaturized version of full-scale implants, providing a system compatible with conventional analysis methods. We used a fibroblast/vascular endothelial cell co-cultures as our model system and by utilising single microbeads we have quantified the effect of gel microenvironment (degradability, presence of RGD peptides within gel formulation) on cell behaviour and the effect of the titanium presence on cell behaviour and gel formation. Titanium presence slightly changed gel properties without hindering gel formation or affecting cell viability. Cells showed a preference to move towards the titanium beads and fibroblast proliferation was significantly higher in hybrids compared to gel only controls. The MMP (Matrix Metalloproteinase)-sensitive hydrogels induced sprouting by cells in co-culture configuration which was quantified by fluorescence microscopy, confocal microscopy and qRT-PCR (Quantitative Reverse transcription polymerase chain reaction). When the microhybrid up-scaled to 3D thick structures, cellular localisation in specific areas of the 3D titanium structures was achieved, without decreasing overall cell proliferation compared to titanium only scaffolds. Microhybrids of titanium and hydrogels are useful models for deciding the necessary modifications of metallic implants and they can be used as a modelling system for the study of tissue/titanium implant interactions. Statement of SignificanceThis article demonstrates a method to apply cell-laden hydrogels to porous titanium implants and a model of titanium/hydrogel interaction at micro-level using titanium microbeads. The feasibility of site-specific modification of titanium implants with cell-laden microgels has been demonstrated. Use of titanium microbeads in combination with hydrogels with conventional analysis techniques as described in the article can facilitate the characterisation of surface modification of titanium in a relevant model system.

Injectable, Highly Flexible, and Thermosensitive Hydrogels Capable of Delivering Superoxide Dismutase

Injectable hydrogels are attractive for cell and drug delivery. In this work, we synthesized a family of injectable, biodegradable, fast gelling and thermosensitive hydrogels based on N-isopropylacrylamide (NIPAAm), acrylic acid (AAc), dimethyl-gamma-butyrolactone acrylate (DBA), and 2-hydroxyethyl methacrylate-poly(trimethylene carbontate) (HEMAPTMC) macromer. Type I collagen was composited with the hydrogels to improve their biocompatibility. The hydrogel copolymer solutions were readily injectable at 4 degrees C. The solutions exhibited thermal transition temperatures ranging from 23.6 to 24.5 degrees C and were capable of gelation within 7 s at 37 degrees C to form highly flexible and soft hydrogels with moduli from 39 to 119 KPa and breaking strains >1000%, depending on the copolymer composition and collagen addition. After 2 weeks incubation in PBS, the hydrogels demonstrated weight losses ranging from 10-20%. The completely degraded hydrogels had thermal transition temperatures >40 degrees C and were soluble at body temperature. Superoxide dismutase (SOD) was encapsulated in the hydrogels for the purpose of capturing superoxide within the inflammatory tissue after being delivered in vivo. The hydrogels demonstrated a sustained release profile during a 21-day release period. The release kinetics was dependent on the SOD loading, collagen addition, hydrogel degradation and water content. The released SOD remained bioactive during the entire release period. To test in vitro if the loaded SOD could protect cells encapsulated within the hydrogel from attack by superoxide, human mesenchymal stem cells (MSC) were encapsulated in SOD-loaded hydrogels and cultured in medium containing superoxide generated by activated macrophages. It was found that SOD loading largely suppressed superoxide penetration into the hydrogel and cell membrane. Under normal culture conditions, SOD loading stimulated MSC growth. The SOD-loaded hydrogel exhibited significantly higher cell numbers than the non-SOD loaded hydrogel during a 7-day culture period. These results demonstrated that the developed hydrogels could be used as delivery vehicles for stem cell therapy and drug delivery.

Protein release from injectable stereocomplexed hydrogels based on PEG–PDLA and PEG–PLLA star block copolymers

The release of two model proteins, lysozyme and immunoglobulin G (IgG) from injectable, fast gelling, biodegradable hydrogels composed of PEG–PLLA and PEG–PDLA star block copolymers was investigated. Lysozyme was quantitatively released in 10 days. The release of IgG was slower and after 20 days 40–60% was released depending on the composition of the gel.

Control of Thermogelation Properties of Hydrophobically-Modified Methylcellulose

Aqueous solutions that undergo reversible thermosensitive gelation around body temperature were developed based on hydrophobically-modified methyl cellulose (HMMC). The approach involved HMMC as the main component of aqueous compositions to provide a system with fast gelling properties, which has not been accomplished with aqueous solutions of unmodified methyl cellulose (MC). MC was modified with the stearyl group as a hydrophobic modifier by controlling the degree of modification. The gelation rate of aqueous solutions containing identical amounts of HMMC and NaCl increased as the temperature increased. The HMMC solutions gelled at a fixed temperature and concentration range, while the unmodified MC solutions did not show sol-to-gel transition. In addition, HMMC solutions exhibited much faster gelation than MC solutions at given polymer and NaCl concentrations. The HMMC/NaCl solutions exhibited the reversible gel-to-sol transition upon cooling below 25°C. The rate of sol-to-gel transition at body temperature, and the reversible gel-to-sol transition at room temperature, were modulated by adjusting the concentration of HMMC and NaCl, respectively. The HMMC/NaCl compositions provided a simple system for accurate control of the thermogelling temperature and the thermogelation rates.

Melgisorb: a highly absorbent calcium/sodium alginate dressing.

Alginates have been used in wound care for many years. In recent years alginate dressings have developed to provide an extremely cost-effective way of managing wounds with a moderate to high level of exudate. The dressing gel has traditionally been either soft or firm on removal, but with new technology softness and fast gelling may now be combined with high integrity in a single product. An example of such a product is Melgisorb from Mölnlycke Health Care (the makers of Mepore). Melgisorb is just one dressing in their range of chronic wound care products.