Injectable Materials Research Articles

Granular Disulfide-Crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability Parameters

Granular polymer hydrogels based on dynamic covalent bonds are attracting a great deal of interest for the design of injectable biomaterials. Such materials generally exhibit shear-thinning behavior and properties of self-healing/recovery after the extrusion that can be modulated through the interactions between gel microparticles. Herein, bulk macro-hydrogels based on thiolated-hyaluronic acid were produced by disulphide bond formation using oxygen as oxidant at physiological conditions and gelation kinetics were monitored. Three different thiol substitution degrees (SD%: 65%, 30% and 10%) were selected for hydrogel formation and fully characterized as to their stability in physiological medium and morphology. Then, extrusion fragmentation technique was applied to obtain hyaluronic acid microgels with dynamic disulphide bonds that were subsequently sterilized by autoclaving. The resulting granular hyaluronic hydrogels were able to form stable filaments when extruded through a syringe. Rheological characterization and cytotoxicity tests allowed to assess the potential of these materials as injectable biomaterials. The application of extrusion fragmentation for the formation of granular hyaluronic hydrogels and the understanding of the relation between the autoclaving processes and the resulting particle size and rheological properties should expand the development of injectable materials for biomedical applications.

Optimized TFB-based perovskite quantum dot light emitting diode

Perovskite quantum dots (PQDs) are semiconducting nanocrystals that have been exploited for fabricating light-emitting diodes because of their exciton confinement, high quantum yield, and adjustable color. Therefore, PQD-based Light-emitting diodes (PQDLEDs) have attracted huge attention because of their significant external quantum efficiencies. In our research, to prohibit fluorescence quenching dots which is caused by the connection of the PQDs and hole injection material into the emissive layer and hole injection layer, poly [(9,9- dioctylfluorenyl-2,7-diyl)-co-(4,4’-(N-(pbutylphenyl)) diphenylamine)] (TFB) is utilized which can decrease the hole injection barrier. To reach the TFB's optimal thickness, we control both the precursor solution concentration and the rotational speed during the spin coating process. Finally, we find out that the optimal TFB precursor solution concentration and rotational speed are 8.0 mg ml−1, and 4500 rpm, respectively, which results in 35 nm thickness. The optimized PQDLED turn-on voltage, maximum brightness, maximum external quantum efficiency (EQE) (vs luminance), and maximum current efficiency were 2.2 V, 4522 cd m−2, ∼0.15%, and ∼0.5 cd A−1, respectively.

MECHANICAL PERFORMANCE OF INJECTED STEEL‐REINFORCED RESIN CONNECTORS UNDER DIFFERENT CONFINED CONDITIONS FOR REUSABLE COMPOSITE STRUCTURES

AbstractA novel injection material for the development of demountable injected bolted connections in oversized holes has been recently developed by the Steel and Composite Structure research group at Delft University of Technology [1]. This injection material is a steel‐reinforced resin (SRR) which consists of spherical steel particles embedded in a resin. The SRR proved to have several benefits such as the increase of the stiffness and strength of the connection and the decrease of its creep deformation when compared to injected connections with conventional epoxy resin. Research on the performance of the injected steel‐reinforced resin (iSRR) has been focused on steel‐to‐steel, steel‐to‐concrete, and steel‐to‐FRP connections. This paper presents an overview of the recent experimental and numerical research on the mechanical properties of demountable iSRR connections and provides a comparison between different confined conditions of the injected volume.

Front Cover: Recent Progress of Organic Semiconductor Materials in Spintronics (Chem. Asian J. 3/2023)

Spintronics, an area focusing on the spin-dependent transport process of electrons, has witnessed a rapid development in recent years. Herein, the progress and working principle of spin valves are reviewed, advances in organic spin injection and transport materials summarized, and the influence of spin interfaces on device performance thoroughly analyzed. Finally, reliable methods for constructing organic spin valve devices are introduced and the challenges faced in the current research of organic spin valves and their future development are discussed. More information can be found in the Review by Yuguang Ma et al.

Experimental method and application of the slurry “diffusion-bleeding-seepage” of isolated overburden grout injection

Isolated overburden grout injection (IOGI) is a green mining method to control surface subsidence. Slurry water significantly influences grouting effectiveness and mining safety. This study establishes a three-dimensional visualization experimental system for slurry “diffusion-bleeding-seepage” to investigate the seepage law of slurry water. The system is composed primarily of a transparent box (1.2 m × 0.5 m × 0.25 m) and support, with the solid–liquid coupling seepage similar material and modules for mining, grouting injection, slurry pressure and displacement monitoring, overburden saturation monitoring, and water leakage monitoring of the working face. A similar material with good permeability and non-disintegration is obtained by hydrophilic, water absorption, and permeability tests. Grouting and mining are simulated by pulling acrylic sheets and pumping slurry. With the fly ash slurry entering the injection layer, the slurry undergoes water–cement separation, and the water bleeding is formed to seep into the similar material. The volumetric water content of the similar material is obtained by arranging multiple groups of volumetric water content sensors into the similar material. The corresponding saturation is obtained by theoretical calculation. The experimental system is used to simulate the seepage of slurry water in a high initial saturation overburden, and the characteristics of injection slurry diffusion and water bleeding are obtained. The profile distribution of seepage of slurry water is found to possess a semi-elliptical shape. Under the condition of high initial saturation, slurry water appears in the working face. The system provides a convenient method for further research of IOGI slurry water seepage.

Effects of Calcium Carbonate Microcapsules and Nanohydroxyapatite on Properties of Thermosensitive Chitosan/Collagen Hydrogels

Thermosensitive chitosan/collagen hydrogels are osteoconductive and injectable materials. In this study, we aimed to improve these properties by adjusting the ratio of nanohydroxyapatite particles to calcium carbonate microcapsules in a β-glycerophosphate-crosslinked chitosan/collagen hydrogel. Two hydrogel systems with 2% and 5% nanohydroxyapatite particles were studied, each of which had varying microcapsule content (i.e., 0%, 1%, 2%, and 5%). Quercetin-incorporated calcium carbonate microcapsules were prepared. Calcium carbonate microcapsules and nanohydroxyapatite particles were then added to the hydrogel according to the composition of the studied system. The properties of the hydrogels, including cytotoxicity and biocompatibility, were investigated in mice. The calcium carbonate microcapsules were 2-6 µm in size, spherical, with rough and nanoporous surfaces, and thus exhibited a burst release of impregnated quercetin. The 5% nanohydroxyapatite system is a solid particulate gel that supports homogeneous distribution of microcapsules in the three-dimensional matrix of the hydrogels. Calcium carbonate microcapsules increased the mechanical and physical strength, viscoelasticity, and physical stability of the nanohydroxyapatite hydrogels while decreasing their porosity, swelling, and degradation rates. The calcium carbonate microcapsules-nanohydroxyapatite hydrogels were noncytotoxic and biocompatible. The properties of the hydrogel can be tailored by adjusting the ratio of calcium carbonate microcapsules to the nanohydroxyapatite particles. The 1% calcium carbonate microcapsules containing 5% nanohydroxyapatite particle-chitosan/collagen hydrogel exhibited mechanical and physical strength, permeability, and prolonged release profiles of quercetin, which were superior to those of the other studied systems and were optimal for promoting bone regeneration and delivering natural flavonoids.

Recent Progress of Organic Semiconductor Materials in Spintronics.

Spintronics, a new discipline focusing on the spin-dependent transport process of electrons, has been developing rapidly. Spin valves are the most significant carriers of spintronics utilizing the spin freedom of electrons. It is expected to pierce "Moore's Law" and become the core component in processors of the next generation. Organic semiconductors advance in their adjustable band gap, weak spin-orbit coupling and hyperfine interaction, excellent film-forming property, having enormous promise for spin valves. Here, the principle of spin valves is introduced, and the history and progress in organic spin injection and transport materials are summarized. Then we analyze the influence of spinterface on device performance and introduce reliable methods of constructing organic spin valves. Finally, the challenges for spin valves are discussed, and the future is proposed. We aim to draw the attention of researchers to organic spin valves and promote further research in spintronics through this paper.

Applications of injectable hemostatic materials in wound healing: principles, strategies, performance requirements, and future perspectives.

Uncontrolled traumatic bleeding can lead to death due to excessive blood loss within minutes. Early intervention is crucial to save lives, making timely and effective hemostasis is a major global challenge. Injectable hemostatic materials (IHMs) have been proposed to improve the effectiveness of hemostasis, facilitate wound healing, and enhance survival rates in emergency situations. The superior hemostatic performance of IHMs has garnered significant attention. However, there are relatively few comprehensive reviews on IHMs. This paper aims to provide a comprehensive review of the latest research progress on IHMs in recent years. Firstly, the physiological hemostatic process and the underlying principles of hemostasis are analyzed. Subsequently, the synthesis strategies for different IHMs are discussed. The performance requirements of IHMs are then summarized, including high efficiency, biocompatibility, degradability, manipulability, stability and antibacterial ability. Finally, the development prospects and challenges of IHMs are presented. This review serves as a necessary and systematic summary of IHMs, providing a valuable reference for the development of new high-performance hemostatic materials and their practical clinical applications.

Analyzing the characteristics of degraded glucomannan of <i>Amorphophallus oncophyllus</i> using hydrogen peroxide and ultrasonication

<abstract> <p>Glucomannan, one of the viscous polysaccharides, has been applied for various purposes in food industries. However, its high viscosity limits glucomannan in some applications e.g., as an injectable material and encapsulant in the spray drying method. Hence, glucomannan modification is needed to fulfill specific characteristics in such applications. This study investigated the modification of glucomannan properties under degradation treatment using hydrogen peroxide and ultrasonication in ethanol solvent. The modifications of glucomannan were conducted in a 35% hydrogen peroxide solution for 4 h and 40 kHz ultrasonication in 50% ethanol solvent. The combination of ultrasonication and oxidation significantly reduced the glucomannan viscosity, molecular weight, and swelling but increased the solubility. The oxidation, ultrasonication, or their combination approach increased carbonyl content, whiteness, and syneresis. The degradation created a coarse surface on the glucomannan particles. Interestingly, although the oxidation or the ultrasonication reduced glucomannan crystallinity, the combination of both methods increased this property. This result confirmed the synergetic treatments of the oxidation using hydrogen peroxide and the ultrasonication could effectively modify the properties of glucomannan including reducing the viscosity to the level that allowed the glucomannan to be spray-dried.</p> </abstract>

Injectable and photocurable macromonomers synthesized using a heterometallic magnesium-titanium metal-organic catalyst for elastomeric polymer networks.

Injectable and in situ photocurable biomaterials are receiving a lot of attention due to their ease of application via syringe or dedicated applicator and ability to be used in laparoscopic and robotic minimally invasive procedures. The aim of this work was to synthesize photocurable ester-urethane macromonomers using a heterometallic magnesium-titanium catalyst, magnesium-titanium(iv) butoxide for elastomeric polymer networks. The progress of the two-step synthesis of macromonomers was monitored using infrared spectroscopy. The chemical structure and molecular weight of the obtained macromonomers were characterized using nuclear magnetic resonance spectroscopy and gel permeation chromatography. The dynamic viscosity of the obtained macromonomers was evaluated by a rheometer. Next, the photocuring process was studied under both air and argon atmospheres. Both the thermal and dynamic mechanical thermal properties of the photocured soft and elastomeric networks were investigated. Finally, in vitro cytotoxicity screening of polymer networks based on ISO10993-5 revealed high cell viability (over 77%) regardless of curing atmosphere. Overall, our results indicate that this heterometallic magnesium-titanium butoxide catalyst can be an attractive alternative to commonly used homometallic catalysts for the synthesis of injectable and photocurable materials for medical applications.

An injectable curcumin-releasing organohydrogel with non-drying property and high mechanical stability at low-temperature for expedited skin wound care

Although hydrogels have demonstrated great potential as new wound dressing materials, their instability in shape and/or mechanical characteristics due to water loss or freezing remains a shortcoming for wound care application. Herein, a novel injectable organohydrogel (IOH) of physically crosslinked PVA/glycerol that possesses non-drying capability and high stability at low temperature was developed for wound care. IOH has a skin-like stiffness ( G' , ∼280 Pa), high injectability, self-healing capability, high water-vapor transmission rate, and bacterial inhibitory effect. IOH exhibits high shape and mechanical stabilities after curing at 37 °C and 50% relative humidity for 7 days or after curing at –20 °C for 1 day. In addition, glycerol in IOH enabled an efficient loading and release of water-insoluble curcumin, a well-known anti-bacterial and anti-inflammation drug. The curcumin-releasing IOH (Cur-IOH) demonstrated significantly enhanced anti-bacterial performance compared to IOH or curcumin-loading polyvinyl alcohol (PVA) hydrogel. More importantly, Cur-IOH could accelerate wound healing in a murine full-thickness skin defect wound model, revealing improved wound contraction, collagen deposition, angiogenesis, and epidermis formation. This study demonstrates the great potential of organohydrogel for the reparation of severe wounds and Cur-IOH as a new type of injectable wound healing material.

9 - Wet and dry challenge of four injectable composite materials

9 - Wet and dry challenge of four injectable composite materials

Chemical signal regulated injectable coacervate hydrogels.

In the quest for stimuli-responsive materials with specific, controllable functions, coacervate hydrogels have become a promising candidate, featuring sensitive responsiveness to environmental signals enabling control over sol-gel transitions. However, conventional coacervation-based materials are regulated by relatively non-specific signals, such as temperature, pH or salt concentration, which limits their possible applications. In this work, we constructed a coacervate hydrogel with a Michael addition-based chemical reaction network (CRN) as a platform, where the state of coacervate materials can be easily tuned by specific chemical signals. We designed a pyridine-based ABA triblock copolymer, whose quaternization can be regulated by an allyl acetate electrophile and an amine nucleophile, leading to gel construction and collapse in the presence of polyanions. Our coacervate gels showed not only highly tunable stiffness and gelation times, but excellent self-healing ability and injectability with different sized needles, and accelerated degradation resulting from chemical signal-induced coacervation disruption. This work is expected to be a first step in the realization of a new class of signal-responsive injectable materials.

Assessment of Injection Safety Practice in Health Care Settings: a Case from the Gambia

Unsafe injection practices transmit bloodborne pathogens on a large scale worldwide and thus the Ministry of Health was assisted in conducting an assessment of injection safety in the Gambia in 2021. Interviews and observation of injection practices in all of the public health facilities and a sample of private health facilities including NGO. A total of 81 health facilities had been involved. Sterilisation of injection material observed in 3 facilities (3.7%) for therapeutic injection. Vaccinations, used either AD syringe (83.7%) or disposable syringes (16.3%). Re-used injection equipment without sterilisation in facilities was 8.6%. Proportion of health facilities in lack of AD syringes is 6.3%. 87.3% of the health facilities the availability of AD syringes was over than 50 units. Lack of disposable syringes was 17.3% of the health facilities. In 46 health facilities (56.8%), the availability of disposable syringes was over 20 units. Lack of safety box in facilities was 50.6% (n=41). Needle stick injuries have been observed in 79.7% (n=74) of the health facilities. A proportion of 70.9% of vaccinators and 52.1% of curative injection providers reported experiencing at least one needle-stick injury. Lack of safety boxes and waste disposable facilities, unsafe behaviours and poor sharp waste management lead to unsafe injection practices in the Gambia, exposing patients, health care workers and community to bloodborne infections. A coordinated strategy, training of health workers, and encouraging of the proper disposal of sharp required to prevent injection-associated infections in the Gambia. Keywords: AD syringes, Injection, Needles, Safety boxes.

Boundary-integral analysis of a 3-d problem for a body with a periodic array of flexible inclusions

The static problem of discontinuous loading of an elastic body with a periodic array of flexible inclusions is considered. The problem is reduced to solving a 2-D boundary integral equation of the second kind of the Newton potential type with respect to an unknown inclusion opening function. With the help of solutions of the equation, the static stress intensity factors mode I are determined and their dependences on the distance between defects, the contrast between the rigidity of the matrix and the inclusion, and the filling of cracks with the injection material are analyzed.

Anti-Osteoarthritic Effects of Cartilage-Derived Extracellular Matrix in a Rat Osteoarthritis Model.

The extracellular matrix (ECM) has many functions, such as segregating tissues, providing support, and regulating intercellular communication. Cartilage-derived ECM (CECM) can be prepared via consecutive processes of chemical decellularization and enzyme treatment. The purpose of this study was to improve and treat osteoarthritis (OA) using porcine knee articular CECM. We assessed the rheological characteristics and pH of CECM solutions. Furthermore, we determined the effects of CECM on cell proliferation and cytotoxicity in the chondrocytes of New Zealand rabbits. The inhibitory effect of CECM on tumor necrosis factor (TNF)-α-induced cellular apoptosis was assessed using New Zealand rabbit chondrocytes and human synoviocytes. Finally, we examined the in vivo effects of CECM on inflammation control and cartilage degradation in an experimental OA-induced rat model. The rat model of OA was established by injecting monosodium iodoacetate into the intra-articular knee joint. The rats were then injected with CECM solution. Inflammation control and cartilage degradation were assessed by measuring the serum levels of proinflammatory cytokines and C-telopeptide of type II collagen and performing a histomorphological analysis. CECM was found to be biocompatible and non-immunogenic, and could improve cell proliferation without inducing a toxic reaction. CECM significantly reduced cellular apoptosis due to TNF-α, significantly improved the survival of cells in inflammatory environments, and exerted anti-inflammatory effects. Our findings suggest that CECM is an appropriate injectable material that mediates OA-induced inflammation.

Development of minimally invasive cancer immunotherapy using anti-disialoganglioside GD2 antibody-producing mesenchymal stem cells for a neuroblastoma mouse model

Mouse IgG anti-disialoganglioside GD2 antibody-secreting mouse mesenchymal stem cells (anti-GD2-MSCs) were developed, and their anti-tumor effects were validated in an in vivo neuroblastoma mouse model. Anti-GD2 antibody constructs were generated, incorporating FLAG-tagged single-chain fragment variables against GD2 fused to a linker sequence, and a fragment of a stationary portion was changed from human IgG to mouse IgG and GFP protein. The construct was lentivirally introduced into mouse MSCs. A syngeneic mouse model was established through the subcutaneous transplantation of a tumor tissue fragment from a TH-MYCN transgenic mouse, and the homing effects of anti-GD2-MSCs were validated by In vivo imaging system imaging. The syngeneic model was divided into three groups according to topical injection materials: anti-GD2-MSCs with IL-2, IL-2, and PBS. The tumors were removed, and natural killer (NK) cells were counted. Anti-GD2-MSCs showed homing effects in syngeneic models. The growth rate of subcutaneous tumors was significantly suppressed by anti-GD2-MSCs with IL-2 (p < 0.05). Subcutaneous tumor immunostaining showed an increased NK cell infiltration in the same group (p < 0.01). Anti-GD2-MSCs using mouse IgG showed a homing effect and significant tumor growth suppression in syngeneic models. Anti-GD2-MSC-based cellular immunotherapy could be a novel therapeutic strategy for intractable neuroblastoma.

Bone Formation on Murine Cranial Bone by Injectable Cross-Linked Hyaluronic Acid Containing Nano-Hydroxyapatite and Bone Morphogenetic Protein.

New injection-type bone-forming materials are desired in dental implantology. In this study, we added nano-hydroxyapatite (nHAp) and bone morphogenetic protein (BMP) to cross-linkable thiol-modified hyaluronic acid (tHyA) and evaluated its usefulness as an osteoinductive injectable material using an animal model. The sol (ux-tHyA) was changed to a gel (x-tHyA) by mixing with a cross-linker. We prepared two sol-gel (SG) material series, that is, x-tHyA + BMP with and without nHAp (SG I) and x-tHyA + nHAp with and without BMP (SG II). SG I materials in the sol stage were injected into the cranial subcutaneous connective tissues of mice, followed by in vivo gelation, while SG II materials gelled in Teflon rings were surgically placed directly on the cranial bones of rats. The animals were sacrificed 8 weeks after implantation, followed by X-ray analysis and histological examination. The results revealed that bone formation occurred at a high rate (&gt;70%), mainly as ectopic bone in the SG I tests in mouse cranial connective tissues, and largely as bone augmentation in rat cranial bones in the SG II experiments when x-tHyA contained both nHAp and BMP. The prepared x-tHyA + nHAp + BMP SG material can be used as an injection-type osteoinductive bone-forming material. Sub-periosteum injection was expected.

Effective spin injection into the organic semiconductor PTCDA evaluated by a normalization method

Studies of spin current injection, transport, and interface control have drawn attention recently for efficient organic spintronic devices. In this study, we apply both spin pumping (SP) and the longitudinal spin Seebeck effect (LSSE) to inject spin currents into a π-conjugated organic semiconductor, perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA), and characterize injection and transport by measuring inverse spin Hall voltage VISHE in spin detectors. A normalization factor introduced to SP analysis eliminates a contribution provoked by deviation of spin sources and leads to a more accurate determination of the spin diffusion length in PTCDA. While SP with Permalloy as a spin source is effective in generating detectable VISHE, the LSSE from yttrium iron garnet shows no convincing sign of spin injection. In addition, spin-flip scattering induced by hybrid states undermining electrical spin injection is negligible in SP. These results are attributed to interfaces between spin sources and PTCDA, indicative of the importance of injection methods and material choices.

Synthesis of a novel injectable alginate impression material and impression accuracy evaluation.

This work aimed to synthesize a novel injectable alginate impression material and evaluate its accuracy. Certain proportions of sodium alginate, trisodium phosphate dodecahydrate, potassium fluorotitanate, diatomaceous earth, and other ingredients were dissolved in water and mixed evenly with a planetary centrifugal mixer to obtain a certain viscosity base paste. Certain proportions of calcium sulfate hemihydrate, magnesium oxide, glycerin, and polyethylene glycol (PEG) 400 were mixed evenly with a planetary centrifugal mixer to obtain the reactor paste with the same viscosity as the base paste. The base and reactor pastes were poured into a two-cylinder cartridge at a 2∶1 volume ratio. A gun device was used to accomplish mixing by compressing materials into a mixing tip. The samples were divided into three groups: injectable alginate impression materials (IA group) as the experimental group, and Jeltrate alginate impression materials (JA group) and Silagum-putty/light addition silicone rubber impression materials (SI group) as the two control groups. Scanning electron microscopy (SEM) showed that the injectable alginate impression materials had a denser structure and fewer bubbles than the commercial alginate impression material. The accuracy of the three kinds of impression materials was evaluated by 3D image superposition. The deviations between the three test group models and the standard model (trueness) were 49.58 μm±1.453 μm (IA group), 54.75 μm±7.264 μm (JA group), and 30.92 μm±1.013 μm (SI group). The deviations of the models within each test group (precision) were 85.79 μm±8.191 μm (IA group), 97.65 μm±11.060 μm (JA group), and 56.51 μm±4.995 μm (SI group). Significant differences in trueness and precision were found among the three kinds of impression materials (P<0.05). The accuracy of the new injectable alginate impression material was better than that of the traditional powder-type alginate impression material but worse than that of the addition silicone rubber impression materials. The novel injec-table alginate impression material demonstrated good operation performance and impression accuracy, showing broad application prospect.