Alginate Hydrogel Matrix Research Articles

In-situ preparation of lanthanide luminescent MOF hydrogel for aldehyde detection☆

Metal-organic frameworks (MOFs) usually exist in the state of powder or crystal. When they are exposed to hydrophilic solvents, their structure will change and become unstable. Therefore, it is a challenge to construct MOF materials with tunable mechanical properties. Herein, we report in-situ growth lanthanide metal-organic framework (LnMOF) in sodium alginate (SA) and polyvinyl alcohol (PVA) hydrogel matrix. The prepared composite hydrogel not only displays characteristic lanthanide narrow-band emission under ultraviolet light, but also demonstrates excellent mechanical properties. The addition of LnMOF significantly enhances the compressive strength of the hydrogel (from 0.75 to 7.32 MPa). Furthermore, the composite hydrogel shows highly selective recognition of glutaraldehyde and gaseous formaldehyde at room temperature. The detection limits (LOD) of SP-EuMOF for glutaraldehyde and formaldehyde are 0.27 and 0.22 ppm, respectively. Based on these results, the LnMOF composite hydrogel is deemed to have significant potential as a fluorescent sensor for both glutaraldehyde and formaldehyde detection.

Plant Biomimetic Principles of Multifunctional Soft Composite Development: A Synergistic Approach Enabling Shape Morphing and Mechanical Robustness.

Plant tissues are constructed as composite material systems of stiff cellulose microfibers reinforcing a soft matrix. Thus, they comprise smart and multifunctional structures that can change shape in response to external stimuli due to asymmetrical fiber alignment and possess robust mechanical properties. Herein, we demonstrate the biomimetics of the plant material system using silk fiber-reinforced alginate hydrogel matrix biocomposites. We fabricate single and bilamellar biocomposites with different fiber orientations. The mechanical behavior of the biocomposites is nonlinear, with large deformations, as in plant tissues. In general, the bilamellar system shows increased modulus, strain UTS, and toughness compared to the single-lamellar system for most of the tested orientations. Overall, the biocomposites present a wide range of elastic modulus values (3.0 ± 0.6-104.7 ± 11.3 MPa) and UTS values (0.23 ± 0.04-12.5 ± 2.0 MPa). The bilamellar biocomposites demonstrated shape-transforming abilities with diverse morphing modes, emulating different plant tissues and creating complex shape-morphing structures. These multifunctional biocomposites possess tunable and robust mechanical properties, controllable shape-morphing deformations, and the ability to self-controlled encapsulation, grip, and release objects. By harnessing biomimetic principles, these soft, smart, and multifunctional materials hold potential applications spanning from soft robotics, medicine, and tissue engineering to sensing and drug delivery.

Determination of the effect of iron oxide nanoparticle content in magnetic chitosan/calcium alginate hydrogel matrix on the removal of glyphosate from water

Determination of the effect of iron oxide nanoparticle content in magnetic chitosan/calcium alginate hydrogel matrix on the removal of glyphosate from water

Cu2Se-based injectable hydrogels for synergistic photothermal/gas therapy of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) produces malignant tumours in the oral cavity and adjacent anatomical structures, ranking sixth among the 11 most common malignant tumours in the body. The poor surgical outcomes for OSCC have led to increasing interest in nanomedicines. Major challenges with concentration-dependent therapies include the effective and precise delivery of gases to the lesion and combination with other therapies to achieve precise treatment. Herein, novel Cu2Se nanosheets (Cu2Se NSs) were ingeniously synthesized and enveloped with a thermosensitive nitric oxide (NO) supplier (sodium nitroprusside dihydrate, SNP) within a sodium alginate (ALG) hydrogel matrix to effectively eradicate tumours by combining photothermal therapy (PTT) and gas therapy (GT). The Cu2Se NSs reduced the glutathione (GSH) present in high concentrations to glutathione disulfide (GSSG), effectively killing squamous cell carcinoma cells under 1064 nm laser irradiation. Moreover, the Cu2Se NS hydrogel wrapped with SNP exhibited good NIR-controlled NO release behaviour, thus realizing the combined application of PTT and GT. PTT along with NO release is expected to improve the antitumour effect and provide new solutions for treating OSCC.

In vitro and in vivo evaluation of alginate hydrogel-based wound dressing loaded with green chemistry cerium oxide nanoparticles.

Interactive wound dressings have displayed promising outcomes in enhancing the wound healing process. This study focuses on creating a nanocomposite wound dressing with interactive and bioactive properties, showcasing potent antioxidant effects. To achieve this, we developed cerium oxide nanoparticles utilizing curcumin as both the reducing and capping agent. Characterization techniques such as SEM, EDX, DLS, Zetasizer, FTIR, and XRD were utilized to analyze the cerium oxide nanoparticles synthesized through a green approach. The image analysis on the obtained TEM images showed that the curcumin-assisted biosynthesized CeO2NPs have a size of 18.8 ± 4.1nm. The peaks located at 28.1, 32.7, 47.1, 56.0, 58.7, 69.0, and 76.4 correspond to (111), (200), (220), (311), (222), (400), and (331) crystallographic planes. We applied the Debye-Scherrer equation and observed that the approximate crystallite size of the biosynthesized NPs is around 8.2nm based on the most intensive broad Bragg peak at 28.1°. The cerium oxide nanoparticles synthesized were integrated into an alginate hydrogel matrix, and the microstructure, porosity, and swelling behavior of the resulting wound dressing were assessed. The characterization analyses provided insights into the physical and chemical properties of the green-synthesized cerium oxide nanoparticles and the alginate hydrogel-based wound dressing. In vitro studies demonstrated that the wound dressing based on alginate hydrogel exhibited favorable antioxidant properties and displayed hemocompatibility and biocompatibility. Animal studies conducted on a rat full-thickness skin wound model showed that the alginate hydrogel-based wound dressing effectively accelerated the wound healing process. Overall, these findings suggest that the alginate hydrogel-based wound dressing holds promise as a highly effective material for wound healing applications.

Impact of simulated brain interstitial fluid flow on the chemokine CXCL12 release from an alginate-based hydrogel in a new 3D in vitro model

Introduction: Extensive investigation has been undertaken regarding drug delivery systems for the management of glioblastoma multiforme (GBM). The infiltrative behavior of GBM cells within the brain tissue is primarily attributed to their heterogeneity, the movement of interstitial fluid (IFF), and the presence of chemokines. These factors contribute to the limited effectiveness of current conventional treatments. To address the dissemination of GBM cells, a proposed therapeutic approach involves utilizing a controlled release gradient of CXC-chemokine-ligand-12 (CXCL12). However, the impact of IFF on GBM cell migration within the brain underscores its critical importance as a significant parameter, which, surprisingly, has not been extensively studied in the context of localized drug delivery targeting the brain.Methods: Hydrogels are known for their inherent capacity to entrap various agents and exert precise control over their subsequent release. In the present investigation, we aimed to elucidate the release kinetics of CXCL12, whether in its free form or encapsulated within nanoparticles, from alginate-based hydrogels, both under static and dynamic conditions. To investigate the impact of convective forces mimicking the interstitial fluid flow (IFF) within the peritumoral environment of the brain, a three-dimensional in vitro model was developed. This model enabled the evaluation of CXCL12 release as a function of time and position, specifically accounting for the contribution of simulated IFF on the release behavior.Results: We first demonstrated that the release kinetic profiles under static culture conditions were independent of the initial mass loading and the predominant phenomenon occurring was diffusion. Subsequently, we investigated the release of CXCL12, which was loaded into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded within an alginate hydrogel matrix. Mathematical modeling results also indicated the presence of electrostatic interactions between alginate and CXCL12. The Alg/Chit-NPs effectively slowed down the initial burst release, leading to a reduction in the diffusion coefficient of CXCL12. To further study the release behavior, we developed a perfusion bioreactor with a unique culture chamber designed to recapitulate the peritumoral environment and varied the fluid flow rates at 0.5 µL/min, 3 µL/min, 6.5 µL/min, and 10 µL/min. As the flow rate increased, the cumulative amount of released CXCL12 also increased for all three initial mass loadings. Beyond 3 µL/min, convection became the dominant mechanism governing CXCL12 release, whereas below this threshold, diffusion played a more prominent role.Conclusion: The indirect perfusion flow had a crucial impact on CXCL12 release and distribution inside the hydrogel in and against its direction. This system highlights the importance of considering the IFF in brain targeting delivery system and will be used in the future to study GBM cell behaviors in response to CXCL12 gradient.

Synergistic Occlusion of Doxorubicin and Hydrogels in CaCO3 Composites for Controlled Drug Release

Extensive exploration is required to deploy mineralization as a tool to develop low-cost yet efficient sustained drug release systems. Unlike previous studies which directly incorporated drug components in mineralized products, we propose an emerging approach to synthesizing drug-loaded CaCO3 composites, relying on the synergistic occlusion of the molecular solutions comprising both the alginate hydrogel matrices and the associated drug (doxorubicin) in the course of mineralization. Independent tools including a scanning electron microscope and adsorption isotherm were employed to characterize the lyophilized composites, which led to the conclusion that the anticancer drug doxorubicin (DOX) was uniformly dispersed in the hydrogel matrices as a molecular solution. The occlusion strategy led to CaCO3-based composites with high loads and sustained and pH-responsive release of DOX. Considering many drug molecules can form molecular solutions with polymeric components, we find that the synergistic occlusion can become a general approach to designing smart drug delivery systems.

Tunable Conductive Hydrogel Scaffolds for Neural Cell Differentiation.

Multielectrode arrays would benefit from intimate engagement with neural cells, but typical arrays do not present a physical environment that mimics that of neural tissues. It is hypothesized that a porous, conductive hydrogel scaffold with appropriate mechanical and conductive properties could support neural cells in 3D, while tunable electrical and mechanical properties could modulate the growth and differentiation of the cellular networks. By incorporating carbon nanomaterials into an alginate hydrogel matrix, and then freeze-drying the formulations, scaffolds which mimic neural tissue properties are formed. Neural progenitor cells (NPCs) incorporated in the scaffolds form neurite networks which span the material in 3D and differentiate into astrocytes and myelinating oligodendrocytes. Viscoelastic and more conductive scaffolds produce more dense neurite networks, with an increased percentage of astrocytes and higher myelination. Application of exogenous electrical stimulation to the scaffolds increases the percentage of astrocytes and the supporting cells localize differently with the surrounding neurons. The tunable biomaterial scaffolds can support neural cocultures for over 12 weeks, and enable a physiologically mimicking in vitro platform to study the formation of neuronal networks. As these materials have sufficient electrical properties to be used as electrodes in implantable arrays, they may allow for the creation of biohybrid neural interfaces and living electrodes.

The mechanical behavior of silk-fibroin reinforced alginate hydrogel biocomposites - Toward functional tissue biomimetics

Soft tissues are constructed as fiber-reinforced composites consisting of structural mechanisms and unique mechanical behavior. Biomimetics of their mechanical behavior is currently a significant bioengineering challenge, emphasizing the need to replicate structural and mechanical mechanisms into novel biocomposite designs. Here we present a novel silk-based biocomposite laminate constructed from long natural silk and fibroin fibers embedded in an alginate hydrogel matrix. Controlling the mechanical features of these laminates were studied for different fiber volume fractions (VF) and orientations using unidirectional tensile tests. Three material systems were investigated having different fiber orientations: longitudinal (0°), transverse (90°), and cross-plied (0/90°). The general behavior of the biocomposite laminates was anisotropic hyperelastic with large deformations. Longitudinal fibroin laminates have shown a tensile modulus of 178.55 ± 14.46 MPa and tensile strength of 18.47 ± 2.01 MPa for 0.48 VF. With similar VF, cross-plied fibroin laminates demonstrated structural shielding ability, having a tensile modulus and tensile strength of 101.73 ± 8.04 MPa and 8.29 ± 1.63 MPa for only a third of the VF directed in the stretching direction. The stress-strain behavior was in a similar range to highly stiff native human soft tissues such as ligament and meniscus. These findings demonstrate the potential of the fibroin fiber-reinforced biocomposites to mimic the mechanics of tissues with a quantitatively controlled amount of fibers and designed spatial arrangement. This can lead to new solutions for the repair and replacement of damaged functional and highly stiff soft tissues.

Development of Serum-Free Media for Cryopreservation of Hydrogel Encapsulated Cell-Based Therapeutics.

While hydrogel encapsulation of cells has been developed to treat multiple diseases, methods to cryopreserve and maintain the composite function of therapeutic encapsulated cell products are still needed to facilitate their storage and distribution. While methods to preserve encapsulated cells, and post-synthesis have received recent attention, effective preservation mediums have not been fully defined. We employed a two-tiered screen of an initial library of 32 different cryopreservation agent (CPA) formulations composed of different cell-permeable and impermeable agents. Formulations were assayed using dark field microscopy to evaluate alginate hydrogel matrix integrity, followed by cell viability analyses and measurements of functional secretion activity. The structural integrity of large > 1mm alginate capsules were highly sensitive to freezing and thawing in media alone but could be recovered by a number of CPA formulations containing different cell-permeable and impermeable agents. Subsequent viability screens identified two top-performing CPA formulations that maximized capsule integrity and cell viability after storage at -80°C. The top formulation (10% Dimethyl sulfoxide (DMSO) and 0.3M glucose) was demonstrated to preserve hydrogel integrity and retain cell viability beyond a critical USA FDA set 70% viability threshold while maintaining protein secretion and resultant cell potency. This prioritized screen identified a cryopreservation solution that maintains the integrity of large alginate capsules and yields high viabilities and potency. Importantly, this formulation is serum-free, non-toxic, and can support the development of clinically translatable encapsulated cell-based therapeutics. The online version contains supplementary material available at 10.1007/s12195-022-00739-7.

Efficient oral delivery of water-soluble CT contrast agent using an W1/O/W2 alginate hydrogel matrix

HypothesisIohexol (IOH) is a commonly used second-generation nonionic iodinated contrast agent. However, low gastrointestinal mucosal adherence and high downstream speed limit its application in intestinal Computed tomography (CT) imaging. We hypothesize that oral IOH delivery carriers composed of environmentally responsive materials enable the intestinal targeted delivery and prolong the intestinal residence time of IOH, enhancing the intestinal disease detection efficiency. ExperimentsAn emulsion-filled alginate hydrogel system was developed as the intestinal targeting vehicle for IOH. The formulation optimization was determined by response surface analysis. After a thorough study of the physicochemical properties of this hydrogel matrix, the pH sensitivity and the ability to control release were investigated, followed by a vitro cell experiment evaluating its bioactivity and CT imaging capability. FindingsThis alginate hydrogel matrix was sparsely structured and rapidly released IOH at pH 7.4. Meanwhile the swelling degree was 4.4 times higher than that at pH 1.2, indicating a good selective responsiveness to the gastrointestinal simulated environment. It improved the CT visual contrast of A549 cells without affecting cell morphology, suggesting that it would be an effective oral administration for water-soluble nonionic contrast agents and a potential candidate for intestinal disease detection tools.

Impact of internal aqueous phase gelation on in vitro lipid digestion of epigallocatechin gallate‐loaded W 1 /O/W 2 double emulsions incorporated in alginate hydrogel beads

Our objective was to investigate if the internal aqueous phase gelation of Water-in-oil-in-water double emulsions encapsulated in alginate beads would affect their structural stability and lipid hydrolysis during in vitro digestion. Therefore, bioactive molecules such as (-)-epigallocatechin gallate were encapsulated into different types of delivery systems: original double emulsions (as control) and incorporated double emulsions (filled in alginate hydrogel beads), both with non-gelled or gelled internal aqueous phase by locust bean gum and κ-carrageenan. After 2h of gastric digestion, the gelled original emulsions showed smaller mean droplet diameters and less coalescence during the in vitro simulated gastrointestinal digestion compared to the non-gelled original emulsions. For the incorporated emulsions, oil droplets released from beads aggregated under intestinal conditions, and the rate of lipolysis was delayed. Interestingly, the internal aqueous phase gelation also impacted the rate and cumulative amount of free fatty acids (FFA) released. PRACTICAL APPLICATION: The combination of incorporating (-)-epigallocatechin gallate-loaded double emulsions into the alginate hydrogel matrix and gelling the internal aqueous phase was a benefit to regulating the rate and extent of lipid digestion for specific applications in foods, such as to control blood lipid levels and appetite.

A hydrogel spinal dural patch with potential anti-inflammatory, pain relieving and antibacterial effects

CSFL caused by spinal dural defect is a common complication of spinal surgery, which need repair such as suture or sealants. However, low intracranial pressure symptoms, wound infection and prolonged hospital associated with pin-hole leakage or loose seal effect were often occurred after surgical suture or sealants repair. Stable, pressure resistance and high viscosity spinal dural repair patch in wet environment without suture or sealants was highly needed. Herein, a bioactive patch composed of alginate and polyacrylamide hydrogel matrix cross-linked by calcium ions, and chitosan adhesive was proposed. This fabricated patch exhibits the capabilities of promoting defect closure and good tight seal ability with the bursting pressure is more than 790 mm H2O in wet environment. In addition, the chitosan adhesive layer of the patch could inhibit the growth of bacterial in vitro, which is meaningful for the postoperative infection. Furthermore, the patch also significantly reduced the expression of GFAP, IBA-1, MBP, TNF-α, and COX-2 in early postoperative period in vivo study, exerting the effects of anti-inflammatory, analgesic and adhesion prevention. Thus, the bioactive patch expected to be applied in spinal dural repair with the good properties of withstanding high pressure, promoting defect closure and inhibiting postoperative infection.

A hyperelastic-damage model to study the anisotropic mechanical behavior of coral-hydrogel bio-composite

In this research, a hyperelastic strain energy function was developed to investigate the anisotropic mechanical behavior of a soft bio-composite containing the coral collagen fibers and alginate hydrogel matrix. This hyperelastic function considers the matrix isotropic response, anisotropic behavior of soft crimpled fibers, and matrix-fiber interaction. The material parameters of the model were assumed as a function of the volume fraction of fibers to consider the fiber content. The published experimental data of matrix and bio-composites with different volume fractions of fibers in different directions were used to find the material parameters. A damage model was developed to take into account the damage of matrix, fibers, and fiber-matrix interaction. Results showed that the interaction contribution increases by increasing the volume fraction of fibers due to the crosslinks between the matrix and fibers. Moreover, by exceeding the fibers volume fraction from 20%, the anisotropic stiffening dominates the interaction stiffening in the longitudinal test owing to the load-bearing of soft fibers. Simulation results exhibited that cross-plied bio-composites show more uniform deformations than angle-plied bio-composites. Moreover, the damage results showed that the matrix plays a significant role in the failure of bio-composites.

Precise Tuning of Polymeric Fiber Dimensions to Enhance the Mechanical Properties of Alginate Hydrogel Matrices.

Hydrogels based on biopolymers, such as alginate, are commonly used as scaffolds in tissue engineering applications as they mimic the features of the native extracellular matrix (ECM). However, in their native state, they suffer from drawbacks including poor mechanical performance and a lack of biological functionalities. Herein, we have exploited a crystallization-driven self-assembly (CDSA) methodology to prepare well-defined one-dimensional micellar structures with controlled lengths to act as a mimic of fibrillar collagen in native ECM and improve the mechanical strength of alginate-based hydrogels. Poly(ε-caprolactone)-b-poly(methyl methacrylate)-b-poly(N, N-dimethyl acrylamide) triblock copolymers were self-assembled into 1D cylindrical micelles with precise lengths using CDSA epitaxial growth and subsequently combined with calcium alginate hydrogel networks to obtain nanocomposites. Rheological characterization determined that the inclusion of the cylindrical structures within the hydrogel network increased the strength of the hydrogel under shear. Furthermore, the strain at flow point of the alginate-based hydrogel was found to increase with nanoparticle content, reaching an improvement of 37% when loaded with 500 nm cylindrical micelles. Overall, this study has demonstrated that one-dimensional cylindrical nanoparticles with controlled lengths formed through CDSA are promising fibrillar collagen mimics to build ECM scaffold models, allowing exploration of the relationship between collagen fiber size and matrix mechanical properties.

Bioprinting of Regenerative Photosynthetic Living Materials

AbstractLiving materials, which are fabricated by encapsulating living biological cells within a non‐living matrix, have gained increasing attention in recent years. Their fabrication in spatially defined patterns that are mechanically robust is essential for their optimal functional performance but is difficult to achieve. Here, a bioprinting technique employing environmentally friendly chemistry to encapsulate microalgae within an alginate hydrogel matrix is reported. The bioprinted photosynthetic structures adopt pre‐designed geometries at millimeter‐scale resolution. A bacterial cellulose substrate confers exceptional advantages to this living material, including strength, toughness, flexibility, robustness, and retention of physical integrity against extreme physical distortions. The bioprinted materials possess sufficient mechanical strength to be self‐standing, and can be detached and reattached onto different surfaces. Bioprinted materials can survive stably for a period of at least 3 days without nutrients, and their life can be further extended by transferring them to a fresh source of nutrients within this timeframe. These bioprints are regenerative, that is, they can be reused and expanded to print additional living materials. The fabrication of the bioprinted living materials can be readily up‐scaled (up to ≥70 cm × 20 cm), highlighting their potential product applications including artificial leaves, photosynthetic bio‐garments, and adhesive labels.

Bio-composites reinforced with unique coral collagen fibers: Towards biomimetic-based small diameter vascular grafts

Cardiovascular Diseases (CVDs) are the leading cause of death worldwide. Approximately 31% of all global deaths are caused by CVDs, of which 42% are attributable to coronary artery disease (CAD). CAD is characterized by a narrowing of arteries that restricts the normal blood flow. Over time, surgical intervention is required in severe cases of occlusions and includes implantation of autologous vessels. Today synthetic grafts are used successfully as replacements for blood vessels with a diameter larger than 6 mm. However, they often fail as small-diameter blood vessel replacements.This study introduces a new biocomposite material system consisting of unique and long (cm-scale) collagen fibers derived from soft corals embedded within an alginate hydrogel matrix. The new biocomposite layers were used to fabricate grafts, towards developing a new class of tissue-engineered small-diameter blood vessels. These constructs consisted of both circumferentially and longitudinally oriented collagen fibers. The mechanical properties of the grafts were investigated via a new experimental setup constructed in our lab for this purpose, which applied internal pressure levels of 0–300 mmHg. Similar to native coronary arteries, the biocomposite tubes demonstrated a compliance of 4.88 ± 0.99%/100 mmHg for a physiologic pressure range of 80–120 mmHg. Furthermore, a numerical finite element simulation model is proposed to generate the overall mechanical response of the construct. It is composed of axial and circumferential fibers embedded within the continuum alginate elements. Good prediction is demonstrated when compared with the measured pressure-strain response. Moreover, we examined biocompatibility and cell growth on the collagen fibers. Fibroblast cells proliferated during the experiment that lasted for 32 days and showed aligned configuration with the collagen fiber orientation.The novelty of this study is manifested in the use of naturally derived coral-based long collagen fibers for the development of a new class of tissue-engineered grafts. The proposed novel biocomposite graft demonstrated both mechanical and biological compatibility and can be further developed for small-diameter blood-vessel replacement.

Effect of alginate matrix engineered to mimic the pancreatic microenvironment on encapsulated islet function.

Islet transplantation is emerging as a therapeutic option for type 1 diabetes, albeit, only a small number of patients meeting very stringent criteria are eligible for the treatment because of the side effects of the necessary immunosuppressive therapy and the relatively short time frame of normoglycemia that most patients achieve. The challenge of the immune-suppressive regimen can be overcome through microencapsulation of the islets in a perm-selective coating of alginate microbeads with poly-l-lysine or poly- l-ornithine. In addition to other issues including the nutrient supply challenge of encapsulated islets a critical requirement for these cells has emerged as the need to engineer the microenvironment of the encapsulation matrix to mimic that of the native pancreatic scaffold that houses islet cells. That microenvironment includes biological and mechanical cues that support the viability and function of the cells. In this study, the alginate hydrogel was modified to mimic the pancreatic microenvironment by incorporation of extracellular matrix(ECM). Mechanical and biological changes in the encapsulating alginate matrix were made through stiffness modulation and incorporation of decellularized ECM, respectively. Islets were then encapsulated in this new biomimetic hydrogel and their insulin production was measured after 7 days in vitro. We found that manipulation of the alginate hydrogel matrix to simulate both physical and biological cues for the encapsulated islets enhances the mechanical strength of the encapsulated islet constructs as well as their function. Our data suggest that these modifications have the potential to improve the success rate of encapsulated islet transplantation.

Nanoparticle-directed and ionically forced polyphosphate coacervation: a versatile and reversible core\u2013shell system for drug delivery

A drug encapsulation/delivery system using a novel principle is described that is based on an intra-particle migration of calcium ions between a central Ca2+-enriched nanoparticle core and the surrounding shell compartment. The supply of Ca2+ is needed for the formation of a coacervate shell around the nanoparticles, acting as the core of drug-loadable core–shell particles, using the physiological inorganic polymer polyphosphate (polyP). This polyanion has the unique property to form, at an alkaline pH and in the presence of a stoichiometric surplus of calcium ions, water-insoluble and stabile amorphous nanoparticles. At neutral pH a coacervate, the biologically active form of the polymer, is obtained that is composed of polyP and Ca2+. The drug-loaded core–shell particles, built from the Ca–polyP core and the surrounding Ca–polyP shell, were fabricated in two successive steps. First, the formation of the nanoparticle core at pH 10 and a superstoichiometric 2:1 molar ratio between CaCl2 and Na–polyP into which dexamethasone, as a phosphate derivative, was incorporated. Second, the preparation of the coacervate shell, loaded with ascorbic acid, by exposure of the Ca–polyP core to soluble Na–polyP and L-ascorbate (calcium salt). EDX analysis revealed that during this step the Ca2+ ions required for coacervate formation migrate from the Ca–polyP core (with a high Ca:P ratio) to the shell. Electron microscopy of the particles show an electron-dense 150–200 nm sized core surrounded by a less sharply delimited electron-sparse shell. The core–shell particles exhibited strong osteogenic activity in vitro, based on the combined action of polyP and of dexamethasone and ascorbic acid, which reversibly bind to the anionic polyP via ionic Ca2+ bonds. Drug release from the particles occurs after contact with a peptide/protein-containing serum, a process which is almost complete after 10 days and accompanied by the conversion of the nanoparticles into a coacervate. Human osteosarcoma SaOS-2 cells cultivated onto or within an alginate hydrogel matrix showed increased growth/viability and mineralization when the hybrid particles containing dexamethasone and ascorbic acid were embedded in the matrix. The polyP-based core–shell particles have the potential to become a suitable, pH-responsive drug encapsulation/release system, especially for bone, cartilage and wound healing.

Activation of peroxymonosulfate using carbon black nano-spheres/calcium alginate hydrogel matrix for degradation of acetaminophen: Fe3O4 co-immobilization and microbial community response

Herein, we focused on the degradation of acetaminophen (ACT) drug in liquid phase by peroxymonosulfate (PMS) activated by carbon black nano-spheres (CBNS). The nanostructured activator was immobilized into calcium alginate hydrogel matrix (CAHM) to avoid the washout of the fine nanostructures. The Langmuir modeling showed an insignificant contribution to the adsorption process in the removal of ACT. The basic pH conditions favored the decomposition of ACT. Among nutrients, the presence of nitrogenous compounds including nitrite, nitrate and ammonium caused a little decrease in the reactor performance, while the addition of phosphate ion improved the efficiency from 76.8% to 81.9%. The results demonstrated the involvement of both SO4•− and •OH radicals in the degradation of ACT and domination of SO4•− radicals in the degradation process. Co-immobilization of the CBNS with electro-synthesized magnetite nanoparticles resulted in not only the enhanced reusability potential but also improved the efficiency of the treatment process to 95.6%. Mineralization efficiency of the process was not remarkable; however, the process produced an effluent with lower toxicity toward the microbial community of the activated sludge.