Alginate hydrogel beads have been extensively investigated as drug delivery systems due to promising gastric environment stability. In the present study, alginate hydrogel beads were prepared with ...Ca2+ or Fe3+ to serve as the loading vehicles for egg yolk low density lipoprotein (LDL)/pectin nanogels. Scanning electron microscope was carried out to confirm the successful incorporation of nanogels into the beads. The FT-IR spectra and swelling ratio analyses proved that incorporation of nanogels did not affect the physicochemical properties of the hydrogel beads. The developed hydrogel beads exhibited pH dependent release of curcumin pre-encapsulated in nanogels, with significant retention of curcumin in gastric condition compared to curcumin encapsulated in nanogels or alginate beads alone. Hydrogel beads prepared with low viscous alginate and Ca2+ showed limited swelling property and more sustained release of curcumin in simulated gastrointestinal conditions, compared to the beads prepared with high viscous alginate and Fe3+. Gradual dissociation of nanogels from the beads during incubation in simulated intestinal fluid was studied with transmission electron microscope. Our study demonstrated the promising potential of alginate beads as a carrier to protect LDL-based nanogels from destabilization in gastric condition, thus expanding their applications as oral delivery system.
•Egg yolk LDL/pectin nanogels were incorporated into alginate hydrogel beads•Incorporation of nanogels into beads was affected by the types of cation and alginate used to prepare beads•LDL/pectin nanogels exhibited enhanced stability against aggregation during preparation of and loading into the beads•Incorporation of nanogels did not alter the physicochemical properties of beads.•Sustained kinetic release in simulated gastrointestinal fluids was achieved and verified by TEM.
Articular cartilage damage poses huge burden on healthcare sector globally due to its extremely weak inherent regenerative ability. Three‐dimensional (3D) bioprinting for development of cartilage ...mimic constructs using composite bioinks serves as an emerging perspective. However, difficulty in development of suitable bioink and chemical crosslinking associated inherent toxicity hamper widespread adoption of this technique. To circumvent this, a photo‐polymerizable hydrogel‐based bioink which helps in recapitulation of the complex cartilage microenvironment is pertinent. Herein, a photo‐crosslinkable bioink containing different concentrations of silk methacrylate (SilMA) and polyethylene glycol diacrylate (PEGDA) was mixed with chondrocytes for biofabrication of 3D bioprinted cartilage constructs. The rheological properties, printability of bioink and physico‐chemical characterization of printed hydrogel constructs were examined along with cartilaginous tissue formation. The printed SilMA‐PEGDA hydrogel constructs possessed proper internal porous structure and demonstrated most reliable rheological properties, printability along with good mechanical, and degradation properties suitable for cartilage regeneration. Live/dead staining showed cytocompatibility of the 3D‐bioprinted SilMA‐PEGDA constructs. Moreover, a marked increase in cell number and DNA content was observed within the cartilaginous tissue as indicated by cell viability and DNA content quantitation. Biochemical evaluation confirmed the neocartilage formation within SilMA‐PEGDA bioprinted constructs as revealed by enhanced deposition of cartilage specific extracellular matrix‐sulphated GAG (sGAG) and collagen type II (>2‐fold increase, p < 0.001) with time. Finally, immunohistochemical analysis indicated expression of collagen type II and aggrecan which corroborated with cartilaginous tissue formation. Taken together, we conclude that SilMA‐PEGDA bioink could be suitable candidate for bioprinting chondrocytes to support cartilage tissue repair and regeneration.
Growing cells within an extracellular matrix-like 3D gel is required for, or can improve, the growth of many cell types ex vivo. Here, we describe a protocol for the generation of well-defined ...matrices for the culture of intestinal stem cells (ISCs) and intestinal organoids. These matrices comprise a poly(ethylene glycol) (PEG) hydrogel backbone functionalized with minimal adhesion cues including RGD (Arg-Gly-Asp), which is sufficient for ISC expansion, and laminin-111, which is required for organoid formation. As such, the hydrogels present a defined and reproducible, but also tunable, environment, allowing researches to manipulate physical and chemical parameters, and examine their influence on ISC and organoid growth. Hydrogels are formed by an enzymatic cross-linking reaction of multiarm PEG precursors bearing glutamine- and lysine-containing peptides. PEG precursors containing either stable or hydrolytically degradable moieties are used to produce mechanically softening hydrogels, which are used for the expansion of ISCs or the formation of organoids, respectively. We also provide protocols for immunofluorescence analysis of cellular structures grown within these matrices, as well as for their dissociation and retrieval of cells for downstream use. Hydrogel precursors can be produced and their mechanical properties characterized to ascertain stiffness within 5-7 d. Hydrogel formation for ISC expansion or organoid formation takes 1-2 h. The materials described here can be readily adapted for the culture of other types of normal or transformed organoid structures.
Soy lecithin liposomes (SLP) were prepared and partially surface modified with methoxy polyethylene glycol‐cholesterol conjugate (mPEG‐Chol) to improve its poorly‐soluble‐water‐anticancer‐drugs ...delivery efficiency. Paclitaxel (PTX) was used as the model drug and the PTX/SLP@mPEG was successfully developed with the optimal mass ratio of mPEG‐Chol determined at 4% in the SLP@mPEG formulation. The optimal SLP@mPEG formulation had a particle size range of 161.80 ± 1.51 nm and a negative surface charge of −54.30 ± 1.40 mV. Besides, a sustained drug release profile of 72 h and an encapsulation efficiency of 87.48 ± 0.70% was recorded. Moreover, in vitro cytotoxicity assays demonstrated that SLP@mPEG is nontoxic and cytocompatible. Overall, these obtained results provide insights into the potential of SLP@mPEG as a platform for the development of more effective therapies against cancers.
Methoxy polyethylene glycol–cholesterol conjugate was synthesized by a simplistic two‐step chemical reaction involving two intermediates, which was hypothesized to aid in the anti‐cancer‐drug‐ paclitaxel‐ delivering process of soy lecithin liposomal system. Evaluation of the successful synthesized mPEG‐Chol was confirmed by 1H‐NMR and the final product, PTX/SLP@mPEG shown enhanced poorly water‐soluble anticancer drug delivery with its properties characterized and examined by in vitro drug release as well as cellular cytotoxicity.
A photoresponsive hybrid alginate hydrogel was successfully prepared by Ca(2+)-mediated crosslinking reaction with a mixture of β-cyclodextrin-grafted alginate (β-CD-Alg) and diazobenzene-modified ...poly(ethylene glycol) (Az2-PEG). The water-soluble Az2-PEG exhibits efficient trans-to-cis isomerization of the terminal azobenzene moieties under UV-light irradiation and readily switched back to the initial trans state under visible light. Because of low affinity between β-CD and cis-Az, the host-guest inclusion complex formed by β-CD and trans-Az gradually dissociates under UV-light exposure. Accordingly, the bulk gel exhibits substantial photo-induced transformation in gel morphology by the appearance of significant comb-like cavities. This photosensitive behavior accompanied by the structural degradation enables the rapid release of entrapped dye molecules under UV light stimulus. Moreover, an incident light with higher power and mild acidic environment are capable of accelerating the photo-triggered release, thus allowing the potential applications toward acute wound healing.
There is a significant cost to mitigate the infection and inflammation associated with the implantable medical devices. The development of effective antibacterial and anti‐inflammatory biomaterials ...with novel mechanism of action has become an urgent task. In this study, a supramolecular polymer hydrogel is synthesized by the copolymerization of N‐acryloyl glycinamide and 1‐vinyl‐1,2,4‐triazole in the absence of any chemical crosslinker. The hydrogel network is crosslinked through the hydrogen bond interactions between dual amide motifs in the side chain of N‐acryloyl glycinamide. The prepared hydrogels demonstrate excellent mechanical properties—high tensile strength (≈1.2 MPa), large stretchability (≈1300%), and outstanding compressive strength (≈11 MPa) at swelling equilibrium state. A simulation study elaborates the changes of hydrogen bond interactions when 1‐vinyl‐1,2,4‐triazole is introduced into the gel network. It is demonstrated that the introduction of 1‐vinyl‐1,2,4‐triazole endowes the supramolecular hydrogels with self‐repairability, thermoplasticity, and reprocessability over a lower temperature range for 3D printing of different shapes and patterns under simplified thermomelting extrusion condition. In addition, these hydrogels exhibit antimicrobial and anti‐inflammatory activities, and in vitro cytotoxicity assay and histological staining following in vivo implantation confirm the biocompatibility of the hydrogel. These hydrogels with integrated multifunctions hold promising potential as an injectable biomaterial for treating degenerated soft supporting tissues.
A high strength supramolecular polymer hydrogel with multifunctional performances is prepared by copolymerizing N‐arolyoyl glycinamide (NAGA, hydrogen bonding monomer) with 1‐vinyl‐1,2,4‐triazole (VTZ). Triazole residues endow the obtained hydrogels with antibacterial and anti‐inflammatory activities, and dynamic hydrogen bonding contributes to an excellent self‐healability and thermoprocessability. This work offers a simplified way to fabricate antibacterial biohydrogels for treating degenerated load‐bearing tissues.
A versatile point-of-care assay platform was developed for simultaneous detection of multiple targets based on a microfluidic paper-based analytic device (μPAD) using a target-responsive hydrogel to ...mediate fluidic flow and signal readout. An aptamer-cross-linked hydrogel was used as a target-responsive flow regulator in the μPAD. In the absence of a target, the hydrogel is formed in the flow channel, stopping the flow in the μPAD and preventing the colored indicator from traveling to the final observation spot, thus yielding a “signal off” readout. In contrast, in the presence of a target, no hydrogel is formed because of the preferential interaction of target and aptamer. This allows free fluidic flow in the μPAD, carrying the indicator to the observation spot and producing a “signal on” readout. The device is inexpensive to fabricate, easy to use, and disposable after detection. Testing results can be obtained within 6 min by the naked eye via a simple loading operation without the need for any auxiliary equipment. Multiple targets, including cocaine, adenosine, and Pb2+, can be detected simultaneously, even in complex biological matrices such as urine. The reported method offers simple, low cost, rapid, user-friendly, point-of-care testing, which will be useful in many applications.
Mosquito-borne diseases continue to remain major threats to human and animal health and impediments to socioeconomic development. Increasing mosquito resistance to chemical insecticides is a great ...public health concern, and new strategies/technologies are necessary to develop the next-generation of vector control tools. We propose to develop a novel method for mosquito control that employs nanoparticles (NPs) as a platform for delivery of mosquitocidal dsRNA molecules to silence mosquito genes and cause vector lethality. Identifying optimal NP chemistry and morphology is imperative for efficient mosquitocide delivery. Toward this end, fluorescently labeled polyethylene glycol NPs of specific sizes, shapes (80 nm x 320 nm, 80 nm x 5000 nm, 200 nm x 200 nm, and 1000 nm x 1000 nm) and charges (negative and positive) were fabricated by Particle Replication in Non-Wetting Templates (PRINT) technology. Biodistribution, persistence, and toxicity of PRINT NPs were evaluated in vitro in mosquito cell culture and in vivo in Anopheles gambiae larvae following parenteral and oral challenge. Following parenteral challenge, the biodistribution of the positively and negatively charged NPs of each size and shape was similar; intense fluorescence was observed in thoracic and abdominal regions of the larval body. Positively charged NPs were more associated with the gastric caeca in the gastrointestinal tract. Negatively charged NPs persisted through metamorphosis and were observed in head, body and ovaries of adults. Following oral challenge, NPs were detected in the larval mid- and hindgut. Positively charged NPs were more efficiently internalized in vitro than negatively charged NPs. Positively charged NPs trafficked to the cytosol, but negatively charged NPs co-localized with lysosomes. Following in vitro and in vivo challenge, none of the NPs tested induced any cytotoxic effects.
The increased need for wearable and implantable medical devices has driven the demand for electronics that interface with living systems. Current bioelectronic systems have not fully resolved ...mismatches between engineered circuits and biological systems, including the resulting pain and damage to biological tissues. Here, salt/poly(ethylene glycol) (PEG) aqueous two‐phase systems are utilized to generate programmable hydrogel ionic circuits. High‐conductivity salt‐solution patterns are stably encapsulated within PEG hydrogel matrices using salt/PEG phase separation, which route ionic current with high resolution and enable localized delivery of electrical stimulation. This strategy allows designer electronics that match biological systems, including transparency, stretchability, complete aqueous‐based connective interface, distribution of ionic electrical signals between engineered and biological systems, and avoidance of tissue damage from electrical stimulation. The potential of such systems is demonstrated by generating light‐emitting diode (LED)‐based displays, skin‐mounted electronics, and stimulators that deliver localized current to in vitro neuron cultures and muscles in vivo with reduced adverse effects. Such electronic platforms may form the basis of future biointegrated electronic systems.
Programmable hydrogel ionic circuits completely composed of salt, water, and biofriendly hydrogels are developed based on salt/poly(ethylene glycol) aqueous two‐phase systems. Such systems enable designer electronics that match the properties of biological systems and route high‐resolution ionic electrical signals between engineered and living systems while avoiding tissue damage. Such platforms may form the basis of future biointegrated electronic systems.
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