Alginate Microbeads Research Articles

Extraction of Penicillin G From Dairy Products Using Deep Eutectic Solvent/Alginate Beads Enhanced via Layered Double Hydroxides.

A new nanocomposite based on alginate microbeads impregnated with novel strontium-aluminum layered double hydroxide (Sr-Al LDH) incorporated with choline chloride-urea deep eutectic solvent (ChCl-U DES) was introduced. The microbeads and LDH were characterized by adsorption/desorption isotherms, Fourier-transform infrared spectroscopy, SEM, and x-ray diffraction. The adsorbent was employed for determining penicillin G (PENG) using dispersive solid-phase extraction prior to HPLC analysis. The extraction efficiency of the adsorbent, compared with that of unmodified alginate, showed a 2.5-fold increase. Significant parameters, including elution conditions, sorbent composition and mass, adsorption time, and sample pH, were optimized. The LOD was 0.4µg kg-1, and the linear range was 1.4-500µg kg-1. The LOQ (1.4 µg kg-1) was lower than the established maximum level for PENG by the European Union (4 µg kg-1). Enrichment factor and synthesis reproducibility were also investigated. The method's accuracy was evaluated through PENG analysis in dairy products and water, with recoveries of 81%-107% (RSDs<7.6%). The procedure's greenness was assessed using the Analytical Eco-scale and achieved excellent green credentials. To the best of our knowledge, this is the first report on the synthesis and application of a novel alginate composite for the extraction of PENG from dairy and water samples.

Integration of cadmium sulfide quantum dots with calcium alginate microbeads for dual-functional mercury (II) ion sensing and removal

Mercury contamination poses human health as well as ecosystem at significant risks. This study introduces a novel approach for the selective detection with removal of Hg2+ ions from aqueous media by developing a dual functional adsorbent that combines calcium alginate microbeads (FMCAB) with capped cadmium sulfide quantum dots (CdS QDs). CdS QDs immobilized on calcium alginate microbeads in magnetite facilitated efficient separation from the adsorption system under an external magnetic field. The fluorescence properties of CdS QDs remain largely unaffected before and after adsorption of Hg2+ ions on FMCAB, enabling selective monitoring of these ions. The adsorbent demonstrated a high adsorption capacity of around 160 μg/g and exhibited a quick and effective process. FMCAB evidenced selectivity over the other metal ions with limits of detection 12.9 μM. The results from this research pave the way for novel applications of FMCAB for heavy metal ions sensing probes and its removal.

Sustained BMP-2 delivery via alginate microbeads and polydopamine-coated 3D-Printed PCL/β-TCP scaffold enhances bone regeneration in long bone segmental defects

Background/ObjectiveRepair of long bone defects remains a major challenge in clinical practice, necessitating the use of bone grafts, growth factors, and mechanical stability. Hence, a combination therapy involving a 3D-printed polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) scaffold coated with polydopamine (PDA) and alginate microbeads (AM) for sustained delivery of bone morphogenetic protein-2 (BMP-2) was investigated to treat long bone segmental defects. MethodsSeveral in vitro analyses were performed to evaluate the scaffold osteogenic effects in vitro such as PDA surface modification, namely, hydrophilicity and cell adhesion; cytotoxicity and BMP-2 release kinetics using CCK-8 assay and ELISA, respectively; osteogenic differentiation in canine adipose-derived mesenchymal stem cells (Ad-MSCs); formation of mineralized nodules using ALP staining and ARS staining; and mRNA expression of osteogenic differentiation markers using RT-qPCR. Bone regeneration in femoral bone defects was evaluated in vivo using a rabbit femoral segmental bone defect model by performing radiography, micro-computed tomography, and histological observation (hematoxylin and eosin and Masson's trichrome staining). ResultsThe PDA-coated 3D-printed scaffold demonstrated increased hydrophilicity, cell adhesion, and cell proliferation compared with that of the control. BMP-2 release kinetics assessment showed that BMP-2 AM showed a reduced initial burst and continuous release for 28 days. In vitro co-culture with canine Ad-MSCs showed an increase in mineralization and mRNA expression of osteogenic markers in the BMP-2 AM group compared with that of the BMP-2-adsorbed scaffold group. In vivo bone regeneration evaluation 12 weeks after surgery showed that the BMP-2 AM/PDA group exhibited the highest bone volume in the scaffold, followed by the BMP-2/PDA group. High cortical bone connectivity was observed in the PDA-coated scaffold groups. ConclusionThese findings suggest that the combined use of PDA-coated 3D-printed bone scaffolds and BMP-2 AM can successfully induce bone regeneration even in load-bearing bone segmental defects. The translational potential of this articleA 3D-printed PCL/β-TCP scaffold was fabricated to mimic the cortical bone of the femur. Along with the application of PDA surface modification and sustained BMP-2 release via AM, the developed scaffold could provide suitable osteoconduction, osteoinduction, and osteogenesis in both in vitro settings and in vivo rabbit femoral segmental bone defect models. Therefore, our findings suggest a promising therapeutic option for treating challenging long bone segmental defects, with potential for future clinical application.

Magnetically responsive micro-clustered calcium phosphate-reinforced cell-laden microbead sodium alginate hydrogel for accelerated osteogenic tissue regeneration

The rising prevalence of bone injuries has increased the demand for minimally invasive treatments. Microbead hydrogels, renowned for cell encapsulation, provide a versatile substrate for bone tissue regeneration. They deliver bioactive agents, support cell growth, and promote osteogenesis, aiding bone repair and regeneration. In this study, we synthesized superparamagnetic iron oxide nanoparticles (Sp) coated with a calcium phosphate layer (m-Sp), achieving a distinctive flower-like micro-cluster morphology. Subsequently, sodium alginate (SA) microbead hydrogels containing m-Sp (McSa@m-Sp) were fabricated using a dropping gelation strategy. McSa@m-Sp is magnetically targetable, enhance cross-linking, control degradation rates, and provide strong antibacterial activity. Encapsulation studies with MC3T3-E1 cells revealed enhanced viability and proliferation. These studies also indicated significantly elevated alkaline phosphatase (ALP) activity and mineralization in MC3T3-E1 cells, as confirmed by Alizarin Red S (ARS) and Von Kossa staining, along with increased collagen production within the McSa@m-Sp microbead hydrogels. Immunocytochemistry (ICC) and gene expression studies supported the osteoinductive potential of McSa@m-Sp, showing increased expression of osteogenic markers including RUNX-2, collagen-I, osteopontin, and osteocalcin. Thus, McSa@m-Sp microbead hydrogels offer a promising strategy for multifunctional scaffolds in bone tissue engineering.

Encapsulation of Fennel Essential Oil in Calcium Alginate Microbeads via Electrostatic Extrusion

Fennel essential oil (EO) is well known for its biological activities and wide potential for use in the food, cosmetic, and pharmaceutical industries, where the main challenge is to achieve higher stability of EO. This study aimed to evaluate the potential of electrostatic extrusion for encapsulation of fennel EO by examining the effects of alginate (1%, 1.5%, and 2%) and whey protein (0%, 0.75%, and 1.5%) concentrations and drying methods on the encapsulation efficiency, loading capacity, bead characteristics, and swelling behavior of the produced fennel EO microbeads. Results revealed that electrostatic extrusion proved to be effective for encapsulating fennel EO, with whey protein addition enhancing the examined characteristics of the obtained microbeads. Freeze-drying exhibited superior performance compared to air-drying. Optimal encapsulation efficiency (51.95%) and loading capacity (78.28%) were achieved by using 1.5% alginate and 0.75% whey protein, followed by freeze-drying. GC-MS analysis revealed no differences in the qualitative aspect of the encapsulated and initial EO, with the encapsulated EO retaining 58.95% of volatile compounds. This study highlighted the potential of electrostatic extrusion using alginate and whey protein as a promising technique for fennel EO encapsulation while also emphasizing the need for further exploration into varied carrier materials and process parameters to optimize the encapsulation process and enhance product quality.

Deep learning-assisted concentration gradient generation for the study of 3D cell cultures in hydrogel beads of varying stiffness.

The study of dose-response relationships underpins analytical biosciences. Droplet microfluidics platforms can automate the generation of microreactors encapsulating varying concentrations of an assay component, providing datasets across a large chemical space in a single experiment. A classical method consists in varying the flow rate of multiple solutions co-flowing into a single microchannel (producing different volume fractions) before encapsulating the contents into water-in-oil droplets. This process can be automated through controlling the pumping elements but lacks the ability to adapt to unpredictable experimental scenarios, often requiring constant human supervision. In this paper, we introduce an image-based, closed-loop control system for assessing and adjusting volume fractions, thereby generating unsupervised, uniform concentration gradients. We trained a shallow convolutional neural network to assess the position of the laminar flow interface between two co-flowing fluids and used this model to adjust flow rates in real-time. We apply the method to generate alginate microbeads in which HEK293FT cells could grow in three dimensions. The stiffnesses ranged from 50Pa to close to 1kPa in Young modulus and were encoded with a fluorescent marker. We trained deep learning models based on the YOLOv4 object detector to efficiently detect both microbeads and multicellular spheroids from high-content screening images. This allowed us to map relationships between hydrogel stiffness and multicellular spheroid growth.

Fabrication of silver nanoparticles decorated on sodium alginate microbeads enriched with keratin and investigation of its catalytic and antioxidant activity

In this study, an environmentally friendly, effective, easily synthesizable and recoverable nano-sized catalyst system (Ag@NaAlg-keratin) was designed by decorating Ag nanoparticles on microbeads containing sodium alginate (NaAlg) and keratin obtained from goose feathers. The structure, morphology and crystallinity of the Ag@NaAlg-keratin nanocatalyst were evaluated by XRD, FT-IR, FE-SEM, EDS/EDS mapping and TEM analyses. Catalytic ability of designed Ag@NaAlg-keratin nanocatalyst was then investigated against 4-nitrophenol (4-NP) and methyl orange (MO) reductions. Ag@NaAlg-keratin nanocatalyst effectively reduced 4-NP in 6 min and MO in 5 min, with rate constants of 0.17 min−1 and 0.16 min−1, respectively. Additionally, activation energies (Ea) were found as 39.8 kJ/mol for 4-NP and 37.9 kJ/mol for MO. Performed recyclability tests showed that the Ag@NaAlg-keratin nanocatalyst was easily recovered due to its microbead form and successfully reused five times, maintaining both its activity and structure. Furthermore, antioxidant activity of Ag@NaAlg-keratin nanocatalyst was the highest (73.16 %).

A novel, microfluidic high-throughput single-cell encapsulation of human bone marrow mesenchymal stromal cells

The efficacy of stem-cell therapy depends on the ability of the transplanted cells to escape early immunological reactions and to be retained at the site of transplantation. The use of tissue engineering scaffolds or injectable biomaterials as carriers has been proposed, but they still present limitations linked to a reliable manufacturing process, surgical practice and clinical outcomes. Alginate microbeads are potential candidates for the encapsulation of mesenchymal stromal cells with the aim of providing a delivery carrier suitable for minimally-invasive and scaffold-free transplantation, tissue-adhesive properties and protection from the immune response. However, the formation of stable microbeads relies on the cross-linking of alginate with divalent calcium ions at concentrations that are toxic for the cells, making control over the beads’ size and a single-cell encapsulation unreliable. The present work demonstrates the efficiency of an innovative, high throughput, and reproducible microfluidic system to produce single-cell, calcium-free alginate coatings of human mesenchymal stromal cells. Among the various conditions tested, visible light and confocal microscopy following staining of the cell nuclei by DAPI showed that the microfluidic system yielded an optimal single-cell encapsulation of 2000 cells/min in 2% w/v alginate microcapsules of reproducible morphology and an average size of 28.2 ± 3.7 µm. The adhesive properties of the alginate microcapsules, the viability of the encapsulated cells and their ability to escape the alginate microcapsule were demonstrated by the relatively rapid adherence of the beads onto tissue culture plastic and the cells’ ability to gradually disrupt the microcapsule shell after 24 h and proliferate. To mimic the early inflammatory response upon transplantation, the encapsulated cells were exposed to proliferating macrophages at different cell seeding densities for up to 2 days and the protection effect of the microcapsule on the cells assessed by time-lapse microscopy showing a shielding effect for up to 48 h. This work underscores the potential of microfluidic systems to precisely encapsulate cells by good manufacturing practice standards while favouring cell retention on substrates, viability and proliferation upon transplantation.Graphical

Effect of high‐speed homogenisation on the morphological characteristics and survivability ofLactobacillus rhamnosusGG‐coated microbeads

SummaryXanthan gum can be utilised to overcome the structural defects in alginate microbeads and to improve the stability of microbeads under harsh conditions, that is, high acidic pH and homogenisation speeds. Present study was conducted to assess the survival ofLactobacillus rhamnosusGG using alginate (1.5% w/v) and xanthan gum (0.5% w/v) for encapsulation and structural modifications of microbeads. Homogenisation emulsion technique was used for encapsulation at various homogenisation speeds, that is, 3000 rpm (HS1), 6000 rpm (HS2), 9000 rpm (HS3) and 12 000 rpm (HS4). The resultant microbeads were characterised for diameter, beads yield, structural morphology using the scanning electron microscopy, probiotic count, bacterial survival, storage stability and homogenisation efficiency. Scanning electron microscopy images indicated that the beads produced at 12 000 rpm are more uniform, spherical in shape and have large surface area when compared with the other treatment groups. The diameter of microbeads was reduced from 323.1 to 238.2 μm as the homogenisation speed increased from 3000 to 12 000 rpm. The highest bacterial count (i.e., 9.45 log CFU g−1), homogenisation efficiency (91.6%), beads yield (23.0%), survivability (86.5%) and storage stability (9.84 to 7.90 log CFU g−1) were recorded at 12 000 rpm (HS4). Conclusively, the homogenised encapsulated microbeads at 12 000 rpm significantly improved the beads surface and sphericity, and bacterial survivability.

Encapsulation of Cyclosporine A-Loaded PLGA Nanospheres in Alginate Microbeads for Anti-Inflammatory Application.

The controlled release of cyclosporine A (CsA) microencapsulated in alginate microbeads is a novel drug delivery system for the treatment of inflammatory diseases. In this study, CsA-loaded nanospheres encapsulated in alginate microbeads were applied to evaluate their controlled release profile and anti-inflammatory activity. Initially, a controlled-release drug delivery system was created by encapsulating CsA-loaded PLGA nanospheres within alginate microbeads. CsA-loaded PLGA nanospheres had a diameter of 418.70 ± 59.08 nm, a zeta potential of -22 ± 0.57 mV, and a polydispersity index of 0.517 ± 0.010. CsA-loaded nanosphere-encapsulated alginate microbeads were stable for 37 days. After encapsulating CsA-loaded PLGA nanospheres in the alginate microbeads, 5.60% of CsA was released after 24 h, and approximately 85.90% of the drugs were diffused until day 64. The cytotoxic and anti-inflammatory properties of the CsA released from the microbeads were evaluated in vitro using a murine macrophage cell line (RAW 264.7 cells). CsA-loaded nanosphere-encapsulated alginate microbeads inhibited 39.47 ± 1.71% of nitric oxide production from the RAW 264.7 cells on day 3, whereas nanosphere-encapsulated alginate microbeads inhibited 18.45 ± 1.56% only. CsA released from CsA-loaded nanosphere-encapsulated alginate microbeads had a RAW cell viability of 82.73 ± 5.58% on day 3 compared to 87.59 ± 0.69% of nanosphere-encapsulated alginate microbeads. The efficacy of the CsA-loaded nanosphere-encapsulated alginate microbeads in protecting the immune system via a controlled drug delivery system was established through anti-inflammatory and cell viability evaluation. Based on this research, the controlled release of CsA-loaded nanosphere-encapsulated alginate microbeads provides an innovative treatment for inflammatory diseases.

Alginate Microbeads Containing Halloysite and Layered Double Hydroxide as Efficient Carriers of Natural Antimicrobials.

The present paper describes the preparation and characterization of novel microbeads from alginate filled with nanoclay such as halloysite nanotubes (HNTs). HNTs were used as support for the growth of layered double hydroxide (LDH) crystals producing a flower-like structure (HNT@LDH). Such nanofiller was loaded with grapefruit seed oil (GO), an active compound with antimicrobial activity, up to 50% wt. For comparison, the beads were also loaded with HNT and LDH separately, and filled with the same amount of GO. The characterization of the filler was performed using XRD and ATR spectroscopy. The beads were analyzed through XRD, TGA, ATR and SEM. The functional properties of the beads, as nanocarriers of the active compound, were investigated using UV-vis spectroscopy. The release kinetics were recorded and modelled as a function of the structural characteristics of the nanofiller.

Controlling the size and elastic modulus of in-aqueous alginate micro-beads.

The fabrication of microgels, particularly those ranging from tens to hundreds of micrometers in size, represents a thriving area of research, particularly for biologists seeking controlled and isotropic media for cell encapsulation. In this article, we present a novel and robust method for producing structurally homogeneous alginate beads with a reduced environmental footprint, employing a co-flow focusing microfluidic device. These beads can be easily recovered in an oil-free aqueous medium, making the fabrication method highly suitable for diverse applications. We demonstrate precise control over the production of perfectly spherical beads across a wide range of diameters, from about 30 to 300 μm. We then measure Young's moduli of the beads, revealing a wide accessible range from 90 Pa to 11 kPa, contingent upon controlling the type (e.g. chain length) and concentration of alginate.

Colon Targeted Delivery and In Vitro Evaluation of Curcumin for Colon Cancer

Background:: The second most common cause of mortality by cancer is thought to be colorectal cancer, which is one of the most prevalent tumours in the world. Many health advantages have been linked to curcumin, which is the key component of turmeric. The goal of the current study was to create a colon-targeted microbead method coated with Eudragit S100 to improve cur-cumin targeting in the colon by speeding up the rate of its dissolution Methods: The ionotropic gelation process was used to create the formulations. The surface phe-nomena, bead shape, entrapment effectiveness, drug loading, and in vitro drug release were all as-sessed for formulations. Moreover, calcium alginate beads with an improved core were enteric coat-ed with Eudragit S100. The polymer concentration and curing duration significantly affected parti-cle size and entrapment effectiveness, respectively. Results: The particle size of the improved formulation was 705 μm, drug entrapment efficiency was 83.56%, drug loading was 28.64%, and in vitro release was 81.66% after 6 hours in phosphate buff-er at pH 6.8. After 10 hours, enteric coating with Eudragit S100 of optimized calcium alginate mi-crobeads revealed a 64.09 ± 0.16% drug release. The calculated values of the regression coefficients for the Higuchi, first-order, and zero-order models were 0.9494, 0.8913, and 0.9579, respectively. The 50% inhibitory concentration value was 2.676 based on the percentage of cell viability. Conclusion: To effectively treat colorectal cancer, the enteric-coated calcium alginate microbeads can deliver curcumin selectively to the colon when taken orally.

Formulation and Investigation of CK2 Inhibitor-Loaded Alginate Microbeads with Different Excipients.

The aim of this study was to formulate and characterize CK2 inhibitor-loaded alginate microbeads via the polymerization method. Different excipients were used in the formulation to improve the penetration of an active agent and to stabilize our preparations. Transcutol® HP was added to the drug-sodium alginate mixture and polyvinylpyrrolidone (PVP) was added to the hardening solution, alone and in combination. To characterize the formulations, mean particle size, scanning electron microscopy analysis, encapsulation efficiency, swelling behavior, an enzymatic stability test and an in vitro dissolution study were performed. The cell viability assay and permeability test were also carried out on the Caco-2 cell line. The anti-oxidant and anti-inflammatory effects of the formulations were finally evaluated. The combination of Transcutol® HP and PVP in the formulation of sodium alginate microbeads could improve the stability, in vitro permeability, anti-oxidant and anti-inflammatory effects of the CK2 inhibitor.

3D printing injectable microbeads using a composite liposomal ink for local treatment of peritoneal diseases

The peritoneal cavity offers an attractive administration route for challenging-to-treat diseases, such as peritoneal carcinomatosis, post-surgical adhesions, and peritoneal fibrosis. Achieving a uniform and prolonged drug distribution throughout the entire peritoneal space, though, is difficult due to high clearance rates, among others. To address such an unmet clinical need, alternative drug delivery approaches providing sustained drug release, reduced clearance rates, and a patient-centric strategy are required. Here, we describe the development of a 3D-printed composite platform for the sustained release of the tyrosine kinase inhibitor gefitinib (GEF), a small molecule drug with therapeutic applications for peritoneal metastasis and post-surgical adhesions. We present a robust method for the production of biodegradable liposome-loaded hydrogel microbeads that can overcome the pharmacokinetic limitations of small molecules with fast clearance rates, a current bottleneck for the intraperitoneal (IP) administration of these therapeutics. By means of an electromagnetic droplet printhead, we 3D printed microbeads employing an alginate-based ink loaded with GEF-containing multilamellar vesicles (MLVs). The sustained release of GEF from microbeads was demonstrated. In vitro studies on an immortalized human hepatic cancer cell line (Huh-7) proved concentration-dependent cell death. These findings demonstrate the potential of 3D-printed alginate microbeads containing liposomes for delivering small drug compounds into the peritoneum, overcoming previous limitations of IP drug delivery.Graphical abstract

Alginate microbeads and hydrogels delivering meropenem and bacteriophages to treat Pseudomonas aeruginosa fracture-related infections

Bacteriophage (phage) therapy has shown promise in treating fracture-related infection (FRI); however, questions remain regarding phage efficacy against biofilms, phage-antibiotic interaction, administration routes and dosing, and the development of phage resistance. The goal of this study was to develop a dual antibiotic-phage delivery system containing hydrogel and alginate microbeads loaded with a phage cocktail plus meropenem and evaluate efficacy against muti-drug resistant Pseudomonas aeruginosa. Two phages (FJK.R9–30 and MK.R3–15) displayed enhanced antibiotic activity against P. aeruginosa biofilms when tested in combination with meropenem. The antimicrobial activity of both antibiotic and phage was retained for eight days at 37 °C in dual phage and antibiotic loaded hydrogel with microbeads (PA-HM). In a mouse FRI model, phages were recovered from all tissues within all treatment groups receiving dual PA-HM. Moreover, animals that received the dual PA-HM either with or without systemic antibiotics had less incidence of phage resistance and less serum neutralization compared to phages in saline. The dual PA-HM could reduce bacterial load in soft tissue when combined with systemic antibiotics, although the infection was not eradicated. The use of alginate microbeads and injectable hydrogel for controlled release of phages and antibiotics, leads to the reduced development of phage resistance and lower exposure to the adaptive immune system, which highlights the translational potential of the dual PA-HM. However, further optimization of phage therapy and its delivery system is necessary to achieve higher bacterial killing activity in vivo in the future.

Optimization and In Vitro Evaluation of Curcumin-loaded Calcium Alginate Microbeads using Box-Behnken Design for Colorectal Cancer

Background and Objective:: After lung cancer and breast cancer, colorectal cancer (CRC) is the third most common type of cancer and has the second-highest fatality rate. Curcumin is one such naturally occurring dietary compound that demonstrated promise to treat colon cancer. For that, the goal of the current study was to coat curcumin with Eudragit S100 to treat colorectal cancer in the distal intestine release. The multiparticulate dosage form can increase the solubility of curcumin in the colon environment, sustain the drug release, and protect the drug from abrupt degradation in the colon environment. All of these alterations can enhance the colon tissue levels, especially in the colon cancer cells in the patients, and thereby can enhance the utility of the therapy. Methods:: By using the ionotropic gelation technique, the formulations were made. Moreover, Design Expert 13 used a three-factor, three-level Box-Behnken design (BBD) in this work to optimize the formulation for colon-targeted drug delivery. The concentration of potassium alginate, the concentration of calcium chloride, and the curing duration were considered independent variables, and prepared microbeads were refined to study their impacts on entrapment effectiveness and particle size. Eudragit S100 was enteric coated on Calcium alginate beads with an improved core. Results:: Regarding particle size and entrapment effectiveness, respectively, the polymer concentration and curing duration had a substantial impact. The ideal concentrations of calcium chloride and potassium alginate were 15% w/v and 6% w/v, respectively, with a 20-minute curing time. With a drug entrapment efficiency of 88.4%, the improved formulation had particles with a size of 708 μm. After 12 hours, 79.23±0.32% of the drug was released following an enteric coating of Eudragit S100 of optimized calcium alginate microbeads (10% weight gain). Conclusion:: The present study conclusively demonstrates the usefulness of a Box-Behnken design in the optimization of colon-targeted formulations. To effectively treat colorectal cancer, enteric-coated calcium alginate microbeads can be administered orally to deliver curcumin precisely to the colon.

Short-term function and immune-protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non-human primates without systemic immune suppression: A pilot study.

Replacement of insulin-producing pancreatic beta-cells by islet transplantation offers a functional cure for type-1 diabetes (T1D). We recently demonstrated that a clinical grade alginate micro-encapsulant incorporating the immune-repellent chemokine and pro-survival factor CXCL12 could protect and sustain the integrity and function of autologous islets in healthy non-human primates (NHPs) without systemic immune suppression. In this pilot study, we examined the impact of the CXCL12 micro encapsulant on the function and inflammatory and immune responses of xenogeneic islets transplanted into the omental tissue bilayer sac (OB; n = 4) and diabetic (n = 1) NHPs. Changes in the expression of cytokines after implantation were limited to 2-6-fold changes in blood, most of which did not persist over the first 4 weeks after implantation. Flow cytometry of PBMCs following transplantation showed minimal changes in IFNγ or TNFα expression on xenoantigen-specific CD4+ or CD8+ T cells compared to unstimulated cells, and these occurred mainly in the first 4 weeks. Microbeads were readily retrievable for assessment at day 90 and day 180 and at retrieval were without microscopic signs of degradation or foreign body responses (FBR). In vitro and immunohistochemistry studies of explanted microbeads indicated the presence of functional xenogeneic islets at day 30 post transplantation in all biopsied NHPs. These results from a small pilot study revealed that CXCL12-microencapsulated xenogeneic islets abrogate inflammatory and adaptive immune responses to the xenograft. This work paves the way toward future larger scale studies of the transplantation of alginate microbeads with CXCL12 and porcine or human stem cell-derived beta cells or allogeneic islets into diabetic NHPs without systemic immunosuppression.

Removal of lead and cadmium ions from wastewater using magnetic alginate impregnated sulfur

A new adsorbent, magnetic Fe3O4 sulfonated nanoparticle caged alginate microbeads (S.MNPs@Alg), was developed for Cd(II) and Pb(II) ions removal from water, which could be effectively separated from the solution owing to the superparamagnetic property. This adsorbent was characterized using FTIR, FESEM, XRD, SEM, and VSM. The effect of parameters affecting sorption potential including pH, contact time, and adsorbent dosage was carried out. Under the best experimental condition, the Cd(II) and Pb(II) ions removal efficiencies were reported to be over 95%. To understand the nature of the sorption process, adsorption isotherms including Freundlich and Langmuir models were precisely investigated. The process is fitted well with the Langmuir model and the maximum adsorption capacity obtained was 37 mg. g−1 and 85 mg. g−1 for Cd(II) and Pb(II) ions, respectively. The as-prepared S.MNPs@Alg is easy to prepare and effective in the uptake of Cd(II) and Pb(II) ions with a physisorption mechanism, which adsorption rate is limited with the pseudo-second-order model. The adsorbent lost<5% of its removal efficiency in five adsorption–desorption cycles. Finally, the existence of sulfur groups increased adsorption capacity and decrease the toxicity of magnetic nanoparticles (MNPs) and the presence of magnetism part can facilitate the separation of the adsorbent from the solution.

Development of a small cell lung cancer organoid model to study cellular interactions and survival after chemotherapy.

Introduction: Small-cell-lung-cancer (SCLC) has the worst prognosis of all lung cancers because of a high incidence of relapse after therapy. While lung cancer is the second most common malignancy in the US, only about 10% of cases of lung cancer are SCLC, therefore, it is categorized as a rare and recalcitrant disease. Therapeutic discovery for SCLC has been challenging and the existing pre-clinical models often fail to recapitulate actual tumor pathophysiology. To address this, we developed a bioengineered 3-dimensional (3D) SCLC co-culture organoid model as a phenotypic tool to study SCLC tumor kinetics and SCLC-fibroblast interactions after chemotherapy. Method: We used functionalized alginate microbeads as a scaffold to mimic lung alveolar architecture and co-cultured SCLC cell lines with primary adult lung fibroblasts (ALF). We found that SCLCs in the model proliferated extensively, invaded the microbead scaffold and formed tumors within just 7days. We compared the bioengineered tumors with patient tumors and found them to recapitulate the pathology and immunophenotyping of the patient tumors. When treated with standard chemotherapy drugs, etoposide and cisplatin, we observed that some of the cells survived the chemotherapy and reformed the tumor in the organoid model. Result and Discussion: Co-culture of the SCLC cells with ALFs revealed that the fibroblasts play a key role in inducing faster and more robust SCLC cell regrowth in the model. This is likely due to a paracrine effect, as conditioned media from the same fibroblasts could also support this accelerated regrowth. This model can be used to study cell-cell interactions and the response to chemotherapy in SCLC and is also scalable and amenable to high throughput phenotypic or targeted drug screening to find new therapeutics for SCLC.