Core-shell Hydrogel Research Articles

Mild formation of core–shell hydrogel microcapsules for cell encapsulation

Internal gelation has been an important sol-gel route for the preparation of spherical microgel for drug delivery, cell therapy, or tissue regeneration. Despite high homogeneity and permeability, the internal gelated microgels often result in weak mechanical stability, unregular interface morphology and low cell survival rate. In this work, we have extensively improved the existing internal gelation approach and core–shell hydrogel microcapsules (200–600 μm) with a smooth surface, high mechanical stability and cell survival rate, are successfully prepared by using internal gelation. A coaxial flow-focusing capillary-assembled microfluidic device was developed for the gelation. Rapid gelling behavior of alginate in the internal gelation makes it suitable for producing well-defined and homogenous alginate hydrogel microstructures that serve as the shell of the microcapsules. 2-[4-(2-Hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES) was used in the shell stream during the internal gelation. Thus, a high concentration of acid in the oil solution can be used for better crosslinking the alginate while maintaining high cell viability. We further demonstrated that the gelation conditions in our approach were mild enough for encapsulating HepG2 cells and 3T3 fibroblasts without losing their viability and functionality in a co-culture environment.

Triple Emulsion-Based Rapid Microfluidic Production of Core-Shell Hydrogel Microspheres for Programmable Biomolecular Conjugation.

We report a simple and rapid microfluidic approach to produce core-shell hydrogel microspheres in a single step. We exploit triple emulsion drops with sacrificial oil layers that separate two prepolymer phases, forming poly(ethylene glycol)-based core-shell microspheres via photopolymerization followed by spontaneous removal of the oil layer. Our technique enables the production of monodisperse core-shell microspheres with varying dimensions of each compartment by independently and precisely controlled flow rates. This leads to stable and uniform incorporation of functional moieties in the core compartment with negligible cross-contamination into the shell layer. Selective conjugation of biomolecules is enabled through a rapid bioorthogonal reaction with functional groups in the core compartment with minimal non-specific adsorption. Finally, in-depth protein conjugation kinetics studies using microspheres with varying shell porosities highlight the capability to provide tunable size-selective diffusion barriers by simple tuning of prepolymer compositions for the shell layer. Combined, these results illustrate a significant step forward for programmable high-throughput fabrication of multifunctional hydrogel microspheres, which possess substantial potential in a large array of biomedical and biochemical applications.

Engineering 3D-printed core-shell hydrogel scaffolds reinforced with hybrid hydroxyapatite/polycaprolactone nanoparticles for in vivo bone regeneration.

The versatility of 3D printing has rendered it an indispensable tool for the fabrication of composite hydrogel scaffolds, offering bone biomimetic features through inorganic and biopolymeric components as promising platforms for osteoregeneration. In this work, extrusion-based 3D printing was employed for the realization of osteoconductive composite biopolymer-based hydrogel scaffolds reinforced with hybrid bioactive hydroxyapatite/polycaprolactone nanoparticles (HAp/PCL NPs) for osteoregeneration. The printing technique was optimized for ink printability and viscosity and crosslinking parameters, where a biopolymeric blend of gelatin, polyvinyl alcohol and hyaluronic acid was developed as innovative plain polymeric ink (PPI). Scaffolds were fabricated by 3D printing adopting a biphasic core/shell geometry, where the core phase of the scaffolds was reinforced with HAp/PCL NPs; the scaffolds were then freeze-dried. Novel composite freeze-dried, loaded-core scaffolds, HAp/PCL NPs-LCS-FD exhibited controlled swelling and maintained structural integrity for 28 days. The developed HAp/PCL NPs-LCS-FD also demonstrated double-ranged pore size, interconnected porosity and efficient mechanical stiffness and strength, favorable for osteoconductive actions. Cell infiltration studies, computed tomography and histomorphometry demonstrated that HAp/PCL NPs-LCS-FD afforded osteoconduction, biodegradation, biocompatibility and bone healing in rabbit tibial model, acting as a template for new bone formation. Our findings suggest that HAp/PCL NPs-LCS-FD could offer prominent bone regeneration and could be involved in various bone defects.

A Novel Temperature‐Dependent Hydrogel Emulsion with Sol/Gel Reversible Phase Transition Behavior Based on Polystyrene‐co‐poly(N‐isopropylacrylamide)/Poly(N‐isopropylacrylamide) Core–Shell Nanoparticle

As a kind of temperature-responsive hydrogel, polystyrene-co-poly(N-isopropylacrylamide)/poly(N-isopropylacrylamide) (PS-co-PNIPAM/PNIPAM) core-shell nanoparticles prepared by two-step copolymerization are widely studied and used because of their specific structures and properties. Unlike most reports about the steady stability of PS-co-PNIPAM/PNIPAM core-shell nanoparticle hydrogel emulsion, in this work, the PS-co-PNIPAM/PNIPAM core-shell nanoparticle hydrogel emulsion (symbolized as PS/PNIPAM hydrogel emulsion), which is prepared after the second step of synthesis and without washing out a large number of PNIPAM polymer segments, shows a reversible temperature-dependent sol-gel transition characteristic during the temperature range of 34-80 °C. The PS/PNIPAM hydrogel emulsion is a normal solution at room temperature, and it changes from a sol to a gel statue when the temperature approaches up to low critical solution temperature (LCST). As the temperature continues to increase, the gel (core-shell nanoparticles as the crosslinkers and the linear PNIPAM chain as the 3D gel network) of the PS/PNIPAM hydrogel emulsion gradually shrinks and drains linearly. Compared with most crosslinked hydrogels, the hydrogel here can be arbitrarily changed in shape according to use needs, which is convenient for use, transportation, and storage. Here a new route is provided for the preparation of a PS/PNIPAM core-shell hydrogel nanoparticle system, as well as a new supramolecular crosslinking sol-gel system for application in biomedical materials, sensors, biological separation, drug release, macromolecular adsorption, and purification.

Luer-lock valve: A pre-fabricated pneumatic valve for 3D printed microfluidic automation.

3D printed microfluidic devices are made of stiff and easy-to-fatigue materials and hence are difficult to have robust pneumatic valves. In this work, we describe a type of prefabricated polydimethylsiloxane (PDMS) valves, named the "Luer-lock" valve, which can be incorporated in 3D printed microfluidic devices utilizing the Luer-lock mechanism. Luer-lock design has been adopted for fluidic connections worldwide; it is facile, reliable, and inexpensive. To take advantage of the Luer-lock design, we added "valve ports" to our 3D printed microfluidic devices; prefabricated PDMS valve modules could be embedded into these valve ports, in a leak-free manner, by screwing tight the Luer-locks. In the experiment, we succeeded in fabricating pneumatic valves with a footprint diameter of 0.8 mm and verified the functionality of these valves with a shut-off pressure of 140 mbar and a maximal switching frequency of ∼1 Hz. As a demonstration, we show the serial encoding of core-shell hydrogel microfibers using the Luer-lock valves. Since the Luer-lock valves can be mass-produced and the CAD model of Luer-locks can be easily distributed, we believe that our approach has the potential to be easily adopted by researchers around the globe.

3D culture of functional human iPSC-derived hepatocytes using a core-shell microfiber.

Human iPSC-derived hepatocytes hold great promise as a cell source for cell therapy and drug screening. However, the culture method for highly-quantified hepatocytes has not yet been established. Herein, we have developed an encapsulation and 3D cultivation method for iPSC-hepatocytes in core-shell hydrogel microfibers (a.k.a. cell fiber). In the fiber-shaped 3D microenvironment consisting of abundant extracellular matrix (ECM), the iPSC-hepatocytes exhibited many hepatic characteristics, including the albumin secretion, and the expression of the hepatic marker genes (ALB, HNF4α, ASGPR1, CYP2C19, and CYP3A4). Furthermore, we found that the fibers were mechanically stable and can be applicable to hepatocyte transplantation. Three days after transplantation of the microfibers into the abdominal cavity of immunodeficient mice, human albumin was detected in the peripheral blood of the transplanted mice. These results indicate that the iPSC-hepatocyte fibers are promising either as in vitro models for drug screening or as implantation grafts to treat liver failure.

Synthesis of hollow magnetic carbon microbeads using iron oleate@alginate core-shell hydrogels and their application to magnetic separation of organic dye

The use of biopolymers obtained from natural resources as a carbon source has attracted much attention. In this study, we introduced a novel method for synthesis of hollow magnetic carbon microbeads (HMCMs) based on core-shell alginate hydrogel microbeads consisting of a hydrophobic iron-oleate core encapsulated in a shell of ionically cross-linked alginate hydrogel using the syringe pump with the fabricated double-layered syringe needle. This allows in-situ formation of magnetic particles and carbon walls simultaneously during carbonization. After surface passivation with a silica coating followed by direct carbonization led to in-situ formation of iron oxide particles via the thermal decomposition of the iron-oleate precursor in the core region and a carbon shell derived from the cross-linked alginate polymer during carbonization. The subsequent removal of the silica shell resulted in the formation of HMCMs with a unique surface wrinkle morphology and superparamagnetic property. HMCMs were applied to remove dye from the contaminated wastewater, and the dye-adsorbed HMCMs could be easily removed by an external magnetic field. The proposed synthesis of hollow carbon microbeads can be further optimized to control the size of core-shell microbeads and the components encapsulated in the core and shell, and hence will be useful for preparing diverse types of beads for various applications.

The Belousov-Zhabotinsky Reaction in Thermoresponsive Core-Shell Hydrogel Microspheres with a Tris(2,2'-bipyridyl)ruthenium Catalyst in the Core.

The Belousov-Zhabotinsky (BZ) reaction shows temporal or spatiotemporal structures such as redox oscillation of the catalyst, [ruthenium(II)tris(2,2'-bipyridine)][PF6]2 ([Ru(bpy)3][PF6]2). In this study, autonomously oscillating hydrogel microspheres (microgels) were investigated, which show swelling/deswelling oscillation induced by the redox oscillation of the BZ reaction inside the gel. Despite the periodically and autonomously induced oscillation that does not require an external stimulus, it has not been possible to perform any manipulation of the oscillatory behavior over time. The results of the present study show that it is possible to reversibly switch the microgel oscillations from an "on" active state of the BZ reaction to an "off" inactive state by changing the temperature in combination with thermoresponsive microgels. To realize on-demand switching, the construction of double-shell structures is crucial; the thermoresponsive first shell allows the microgels to modulate the diffusion of the substrates or intermediates in the BZ reaction, while the second shell maintains colloidal stability under high temperatures and high ion concentrations. The functionalized double-shell microgels were prepared via multistep seeded precipitation polymerization. The oscillatory switching behavior of the BZ reaction was observed directly and evaluated by ultraviolet-visible (UV-vis) spectroscopy. The central concept of this study, i.e., "on-off switching" can be expected to benefit the development of advanced bioinspired materials.

3D printed core-shell hydrogel fiber scaffolds with NIR-triggered drug release for localized therapy of breast cancer.

Localized therapy using hydrogels-based drug delivery system (DDS) is a promising strategy for the treatment of diseases such as cancer in superficial tissues. In this study, we presented a facile method to prepare core-shell hydrogel fibers/scaffolds with controlled drug delivery and designed structures for the treatment of the residual breast cancer and prevention of local recurrence after surgery. Mixtures of polydopamine (PDA) and concentrated alginate inks (15.3wt%) as the shell layer, and drug-loaded temperature-sensitive hydrogels as the core part were co-injected and coaxial 3D printed into core-shell hydrogel fibers and scaffolds. Under near infrared (NIR) irradiation, PDA with excellent photothermal effect could raise the temperature of core-shell fibers, which induced the gel-sol transition of the core gels, and subsequently resulted in the drug release from the loosened hydrogel network. The photothermal effect and the released drugs could eliminate cancer effectively. Thus, our prepared core/shell fibers and scaffolds with NIR-triggered on-demand drug release would be promising candidates to fill the cavity of breast tissues after surgical resection of cancer achieving a therapeutic effect for the residual and recurred cancer.

Salivary proteomic profile of patients with renal cell carcinoma.

622 Background: We aimed to explore the salivary proteomic profile (SPP) of patients undergoing surgery for suspected renal cell carcinoma (RCC), then evaluate any significant findings in a validation cohort. Methods: Prospective IRB approved trial of consecutive patients with suspected RCC undergoing curative surgery. Saliva was collected pre- and postoperatively, and from healthy volunteers. Saliva was mixed with sodium orthovanadate and protease inhibitor, aliquoted, and frozen at -80oC. SPP performed using biomarker concentrated saliva via core-shell hydrogel nanoparticles functionalized with molecular baits coupled to high resolution MS/MS electrospray mass spectrometry analysis; output represented as spectral counts. Wilcoxon Rank Sum test was used for comparisons; p-values were adjusted using false discovery rate (FDR) for multiple testing. Results: Exploratory phase: saliva was collected from 27 volunteers and 34 RCC patients (24 clear cell (cc)RCC, 6 chromophobe (ch)RCC, 4 other). Evaluation of cc vs chRCC revealed differential counts for 56 proteins; none were significant after adjustment by FDR. Comparison of matched pre/post-operative SPP in 14 ccRCC patients identified differential counts of 3 proteins: basic salivary proline-rich protein 3 precursor; prolactin-inducible protein precursor; and submaxillary gland androgen-regulated protein 3B precursor. These were not affected by patient age, partial/radical nephrectomy, or tumor size/stage/grade. Validation phase: power analyses indicated a sample size of 38/53 patients = 90% power = effect size of 0.6/0.5, respectively, 2-sided Type 1 error of 0.025. 49 ccRCC patients were enrolled with pre/postop saliva. 611 proteins were identified; none had differential counts after FDR. Conclusions: Using a unique biomarker technology coupled to high resolution MS, interesting SPP’s were seen between RCC subtypes and before/after ccRCC curative resection. We were unable to show significant differences in pre/post-op levels. More research is needed to further study the SPP in RCC patients and the factors impacting their differential expression. In order to aid such efforts, the raw data will be made available for future researchers.

Nanoparticle encapsulated core-shell hydrogel for on-site BMSCs delivery protects from iron overload and enhances functional recovery

The local microenvironment may influence the success of stem cell therapy. Iron overload occurs in many hemorrhagic injuries due to hemolysis and hemoglobin degradation, which not only mediates local cell injury, but also induces damage to the transplanted cells. Here, an injectable nanoparticle encapsulated core-shell hydrogel was fabricated for simultaneous iron overload clearance and bone marrow mesenchymal stem cells (BMSCs) transplantation following intracerebral hemorrhage (ICH). The iron chelator-loaded low-molecular-weight keratin hydrogel with quick degradation property was selected as the outer shell to eliminate iron overload, and BMSCs implantation with high-molecular-weight keratin hydrogel was selected as the inner core. The epidermal growth factor and the basic fibroblast growth factor were entrapped within the poly (lactic-co-glycolic acid) (PLGA) nanoparticle, which was then encapsulated into the core hydrogel to support the BMSC growth and differentiation. The core-shell hydrogel can be easily formed by programmed injections, and the core-shell hydrogel displayed a strong protective effect against the toxicity of hemoglobin in cell experiments. Furthermore, more BMSCs survived in the core-shell hydrogel group in vivo as compared to that in the core hydrogel group and the vehicle group. Less iron deposition and ventricular enlargement, lower brain water content, and faster neurological recovery were also observed. The data demonstrated that this core-shell hydrogel is an effective strategy for promoting transplanted cell survival under the condition of an iron overload.

Self-driven membrane filtration by core–shell polymer composites

A self-driven filtration process based on dynamic core–shell hydrogel absorbers of both high water absorbency and selectivity.

Engineering 3D parallelized microfluidic droplet generators with equal flow profiles by computational fluid dynamics and stereolithographic printing.

Microfluidic droplet generators excel in generating monodisperse micrometer-sized droplets and particles. However, the low throughput of conventional droplet generators hinders their clinical and industrial translation. Current approaches to parallelize microdevices are challenged by the two-dimensional nature of the standard fabrication methods. Here, we report the facile production of three-dimensionally (3D) parallelized microfluidic droplet generators consisting of stacked and radially multiplexed channel designs. Computational fluid dynamics simulations form the design basis for a microflow distributor that ensures similar flow rates through all droplet generators. Stereolithography is the selected technique to fabricate microdevices, which enables the manufacturing of hollow channels with dimensions as small as 50 μm. The microdevices could be operated up to 4 bars without structural damage, including deformation of channels, or leakage of the on-chip printed Luer-Lok type connectors. The printed microdevices readily enable the production of water-in-oil emulsions, as well as polymer containing droplets that act as templates for both solid and core-shell hydrogel microparticles. The cytocompatibility of the 3D printed device is demonstrated by encapsulating mesenchymal stem cells in hydrogel microcapsules, which results in the controllable formation of stem cell spheroids that remain viable and metabolically active for at least 21 days. Thus, the unique features of stereolithography fabricated microfluidic devices allow for the parallelization of droplet generators in a simple yet effective manner by enabling the realization of (complex) 3D designs.

The production of gel beads of soybean hull polysaccharides loaded with soy isoflavone and their pH-dependent release

Core-shell hydrogel beads were successfully produced from soybean hull polysaccharides (SHP). Using electron microscopy, the beads were found to be spherical with smooth surfaces and have tight gel network internal structures. Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction were used to investigate the interaction between soy isoflavone and SHP in the gel beads mesh-like structure. Furthermore, the encapsulation efficiency and loading capacity of gel beads for soy isoflavone are 66.90% and 4.67%, respectively, and have the ability of pH-responsive release in vitro. Through the mathematical model of kinetics, we found that the release of soy isoflavone from gel beads showed Fickian diffusion in release media (pH 2.0 and 7.4), but showed non-Fickian diffusion at pH 4.0 and 6.8. This polymer can be extended to prepare more versatile delivery and controlled release system, appealing for food, pharmaceutical, biomedicine and cosmetics applications.

Biodegradable biopolymer network structures to create delayed burst digestive release of encapsulated lipids

This study sought to investigate whether encapsulation of lipids in core-shell hydrogel structures of tailored shell porosity could create a delayed burst release of encapsulated lipids, and examined the underpinning mechanisms. We demonstrated that gastrointestinal digestion of core-shell structures resulted in a delay in the onset of lipid digestion, without affecting lipid digestion kinetics. Systematic increase in hydrogel protein content above 65 g/L lead to an exponential increase in digestive delay (250 min). Whilst an increase in xanthan content between 5 and 9 g/L lead to a modest decrease in digestive delay (40 min). Rheological investigations revealed a linear relationship between hydrogel storage modulus G′ and digestive breakdown delay (T1/2). Given that G’ is directly related to hydrogel mesh size, this result suggests that the main factor controlling the timing of digestive release is the average mesh size of the outer protein hydrogel. A kinetic model was created to describe the delayed burst release behaviour of encapsulated lipids and successfully predicted the influence of shell thickness, shell protein density on the timing of gastro-intestinal release (in vitro). By combining microstructural/rheological experiments with in vitro digestive studies we have understood the main factors controlling the digestive breakdown of hierarchical biopolymer hydrogels. We could successfully miniaturise these core-shell structures so they would easily empty from the stomach whilst maintaining programmable delayed burst release. We have created a novel family of core-shell hydrogel oral dosage forms for the delivery of poorly soluble drugs and the programmed delivery of lipids within the gut.

Abstract 421: Potential biomarkers for monitoring therapy with Denosumab in patients affected by giant cell tumor of bone

Abstract Giant Cell Tumor (GCT) of Bone is an intramedullary tumor histologically composed by spindle-shaped mononuclear stromal cells, that are the neoplastic and proliferative component of the lesion, and osteoclast-like multinucleated giant cells, that express receptor activator of nuclear factor κB (RANK). The mononuclear stromal cells express RANK ligand, a mediator of osteoclast activation. GCT represents 5% of all bone tumors and 20% of all benign tumors. It usually affects young adults and 2-3% is metastatic, generally to the lung. Curettage is the preferred surgery, while current therapeutic treatment is represented by Denosumab, an anti-RANK-L monoclonal antibody that blocks RANKL binding to RANK, thereby stopping the ‘vicious cycle’ involved in the biological process of GCT. Identification of circulating biomarkers could provide tools for monitoring the effectiveness of therapy and to better understand its biological mechanism. Low molecular weight (LMW) serum proteins or protein fragments, considered to be a rich source of new potential biomarkers and often masked by the presence of abundant proteins, were detected in serum of 25 GCT patients before and after 9 months of treatment with Denosumab, using the hydrogel nanoparticle technique followed by Mass Spectrometry (MS). 25 healthy sera were also analyzed. Hydrogel core-shell nanoparticles selectively entrap LMW proteins by size exclusion and affinity chromatography, protecting them from degradation and amplifying their concentration for subsequent MS detection. Statistical differences in LMW protein abundance between the three groups (GCT pre-treatment, GCT post-treatment, and healthy) were analyzed using the Wilcoxon test or Mann-Whitney U test as appropriate, with the Benjamini-Hochberg False Discovery Rate for multiple test correction. Proteomic analysis revealed 14 differentially expressed analytes in sera from patients pre- and post-treatment, including Complement factor H, Immunoglobulin kappa variable 4-1, Insulin-like growth factor-binding protein 4, Insulin-like growth factor II, Beta-2-glycoprotein 1 and Immunoglobulin lambda constant 6, while 6 proteins were unaltered by the treatment. Furthermore, 52 proteins showed differential abundance in GCT patients before treatment compared to the healthy group, including several (Vitamin D binding protein, Ceruloplasmin, CD5 antigen-like, Serum amyloid A-4 protein, Complement factor D and Apolipoprotein B-100) that we previously identified in a smaller subset of GCT patients and controls, validating our former results. In conclusion, using a noninvasive proteomic technique, we have identified candidate serum biomarkers that could be useful to monitor Denosumab therapy in patients with GCT of bone, for patient management and to better understand its molecular mechanism. Citation Format: Amalia Conti, Alessandra Luchini, Gastone Castellani, Enrico Giampieri, Laura Pazzaglia, Serena Pollino, Giovanna Magagnoli, Emanuela Palmerini, Lance L. Liotta, Piero Picci, Kerry J Rhoden, Maria Serena Benassi. Potential biomarkers for monitoring therapy with Denosumab in patients affected by giant cell tumor of bone [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 421.

Effect of Cyclic Stretch on Tissue Maturation in Myoblast-Laden Hydrogel Fibers.

Engineering of the skeletal muscles has attracted attention for the restoration of damaged muscles from myopathy, injury, and extraction of malignant tumors. Reconstructing a three-dimensional muscle using living cells could be a promising approach. However, the regenerated tissue exhibits a weak construction force due to the insufficient tissue maturation. The purpose of this study is to establish the reconstruction system for the skeletal muscle. We used a cell-laden core-shell hydrogel microfiber as a three-dimensional culture to control the cellular orientation. Moreover, to mature the muscle tissue in the microfiber, we also developed a custom-made culture device for imposing cyclic stretch stimulation using a motorized stage and the fiber-grab system. As a result, the directions of the myotubes were oriented and the mature myotubes could be formed by cyclic stretch stimulation.

Hierarchically structured phase separated biopolymer hydrogels create tailorable delayed burst release during gastrointestinal digestion

The on demand delivery of novel peptide actives, traditional pharmaceuticals, nutrients and/or vitamins is a ever present challenge due to the digestive and metabolic degradation of the active and the delivery vehicle. Biodegradable biopolymer hydrogels have long held promise as candidates for creating tailored release profiles due to the ability to control gel porosity. The present study describes the creation of novel hierarchical biopolymer hydrogels for the controlled release of lipids/lipophilic actives pharmaceutical ingredients (APIs), and mathematically describes the mechanisms that affect the timing of release. The creation of phase separated protein/polysaccharide core (6.6 wt% gelatin, 40 wt% Oil in water emulsion) shell structures (7 g/L xanthan with 70–140 g/L β-lactoglobulin) altered enzyme mass transport processes. This core shell structure enabled the creation of a tailorable burst release of API during gastrointestinal digestion where there is a delay in the onset of release, without affecting the kinetics of release. The timing of the delay could be readily programmed (with release of between 60 and 240 min) by controlling either the thickness or protein concentration (between 70 g/L and 140 g/L β-lactoglobulin) of the outer mixed biopolymer hydrogel shell (7 g/L xanthan with 70–140 g/L β-lactoglobulin). Enzyme diffusion measurements demonstrated that surface erosion was the main degradation mechanism. A kinetic model was created to describe the delayed burst release behaviour of APIs encapsulated within the core, and successfully predicted the influence of shell thickness and shell protein density on the timing of gastro-intestinal release (in vitro). Our work highlights the creation of a novel family of core-shell hydrogel oral dosage forms capable of programmable delivery of lipids/lipophilic APIs. These findings could have considerable implications for the delivery of peptides, poorly soluble drugs, or the programmed delivery of lipids within the gastrointestinal tract.

Numerical Study of Tunable Photonic Nanojets Generated by Biocompatible Hydrogel Core-Shell Microspheres for Surface-Enhanced Raman Scattering Applications.

Core-shell microspheres have been applied in various research areas and, in particular, they are used in the generation of photonic nanojets with suitable design for photonic applications. The photonic nanojet is a narrow and focused high-intensity light beam emitting from the shadow-side of microspheres with tunable effective length, thus enabling its applications in biosensing technology. In this paper, we numerically studied the photonic nanojets brought about from biocompatible hydrogel core-shell microspheres with different optical properties. It was found that the presence of the shell layer can significantly affect the characteristics of the photonic nanojets, such as the focal distance, intensity, effective length, and focal size. Generally speaking, the larger the core-shell microspheres, the longer the focal distance, the stronger the intensity, the longer the effective length, and the larger the focal size of the generated photonic nanojets are. The numerical simulations of the photonic nanojets from the biocompatible core-shell microspheres on a Klarite substrate, which is a classical surface-enhancing Raman scattering substrate, showed that the Raman signals in the case of adding the core-shell microspheres in the system can be further enhanced 23 times in water and 108 times in air as compared in the case in which no core-shell microspheres are present. Our study of using tunable photonic nanojets produced from the biocompatible hydrogel core-shell microspheres shows potential in future biosensing applications.

Microfluidic formation of core-shell alginate microparticles for protein encapsulation and controlled release

Alginate hydrogel particles are promising delivery systems for protein encapsulation and controlled release because of their excellent biocompatibility, biodegradability, and mild gelation process. In this study, a facile microfluidic approach is developed for making uniform core-shell hydrogel microparticles. To address the challenge of protein retention within the alginate gel matrix, poly(ethyleneimine) (PEI)- and chitosan-coated alginate microparticles were fabricated demonstrating improved protein retention as well as controlled release. Furthermore, a model protein ovalbumin was loaded along with delta inulin microparticulate adjuvant into the water-core of the alginate microparticles. Compared to those microparticles with only antigen loaded, the antigen + adjuvant loaded microparticles showed a delayed and sustained release of antigen. This microfluidic approach provides a convenient method for making well-controlled alginate microgel particles with uniform size and controlled properties, and demonstrates the ability to tune the release profiles of proteins by engineering microparticle structure and properties.