Microspheres Research Articles

Demonstrating the impact of Band Gap Modilation on Semiconductor Metal Oxide Gas-sensing Performance

IntroductionGas sensors as the front-end device is the core component of indoor air quality monitoring system and plays an important role in detecting toxic gases. Due to various characteristics of simple structure, all solid state, well stability, and low cost, the semiconducting metal oxides (SMOs) based gas sensors have showed potential [1,2]. Recently, some researches have found that the alteration of electronic band structure will impact the gas sensing characteristics via controlling the charge carrier concentration and enhancing the surface adsorbed oxygen species [2-5].Herein, we reported the synthesis of honeycomb-like 3D inverse opal (IO) CdO-CdGa2O4 microspheres (MS) by using the combination of the one-step USP method with self-assembled S-PS spheres template. Such a novel structure provides both inside and outside reaction sites with high gas accessibility. Since the CdGa2O4 is an n-type semiconductor metal oxide with suitable band gap, and have been found to be a promising material as a transparent electronic conductor [6], we use it as base material of sensitive element. Importantly, the incorporation of CdO with narrow band gap (2.15-2.7 eV) and high electrical conductivity [7] is implied to deeply investigate the relationship between sensing materials’ electronic band structure and gas sensing characteristics. Accordingly, we successfully prepare 3D IO CdO-CdGa2O4 MS based chemiresistor sensor with alterable selectivity and high sensitivity via tuning the ratio of Cd/Ga.Results and ConclusionsIn order to demonstrate the sensing capability of the 3D IO CdGa2O4, CdO-CdGa2O4 MS based gas sensor, we measure their gas sensing response to 100 ppm benzene, toluene, acetone, methanol, formaldehyde, and ethanol, as well as 1 ppm NH3, CH3, H2S, CO, SO2, and NO2 at the range of 175-275 °C, respectively. As shown in Figure 1(A)-(C), the CdGa2O4 based gas sensor exhibits the highest response to 100 ppm formaldehyde at 225 °C, however, after adding of CdO element, the CdO-CdGa2O4 based gas sensor shows lower sensitivity to formaldehyde than primary CdGa2O4 at 225 °C, and possesses higher sensitivity to low concentration of NO2 at 175 °C.Fig.1 (A-C) Gas responses of the 3D IO CdGa2O4, CdO-CdGa2O4 MS based gas sensor to various gases at 175-275 °C, respectively.The UV-vis absorption spectra of the CdGa2O4, CdO-CdGa2O4, and Cd-abundant CdO-CdGa2O4 samples show continuous red shifts of absorption edges with increasing CdO element content (Figure 2(A)), suggesting an decrease in band gap. In addition, the band gaps of all above samples can be calculated from the transformation of UV-vis diffuse reflectance spectra by utilizing the Tauc plot equation (Figure 2(B)). The calculated results further show that the band gaps tend to be narrower values compared with incorporation of CdO (from 4.16 to 2.03 eV). Thus, the baseline resistances in air of Cd-abundant CdO-CdGa2O4 sensor is the lowest (Figure 2(C)). Accordingly, this study indicates that the gas-sensing mechanism of semiconductor metal oxide chemiresistor should consider electron energy level structure. Meantime, we will further study this relationship in subsequent experiments based on above analysis.Fig. 2 (A) UV/visible diffuse reflection spectra and (B) corresponding band gaps of CdGa2O4, CdO-CdGa2O4, and Cd-abundant CdO-CdGa2O4 samples; (C) Resistance in air of gas sensors based on CdGa2O4, CdO-CdGa2O4, and Cd-abundant CdO-CdGa2O4 at 200 °C.

Surface Roughness Effects of Pd‐loaded Magnetic Microspheres on Reduction Kinetics of Nitroaromatics

Metal nanoparticles decoration on magnetically active semiconductor materials is a common strategy to improve the colloidal stability, catalyst harvesting, and reuse. In this study, a surfactant‐free solvothermal method followed by a heat treatment to prepare highly surface roughened α‐Fe2O3 (Hematite)/Pd microspheres (MSPs) is reported. Amine‐functionalized silicate sol‐gel matrix is used as a stabilizing agent for the solvothermal synthesis of Prussian blue (PB) MSPs using HCl at 80 °C for 20 h. It is observed that modulating HCl concentration in a medium led to a high degree of improvement in surface roughness. Employing heat treatment at 350 °C for 6 h, PB MSPs are transformed into α‐Fe2O3, Hematite phase. Fabricated Hematite/Pd MSPs have shown high catalytic reduction activity over p‐nitrophenol. Reduction kinetics of nitroaromatics is monitored using UV‐vis absorption spectroscopy and product formation is confirmed by 1H and 13C NMR analyses.

Bacterial cellulose integrated irregularly shaped microcapsules enhance self-healing efficiency and mechanical properties of green soy protein resins

Soy protein isolate (SPI)-based self-healing thermoset resins were prepared using either poly(DL-lactide-co-glycolide) porous microspheres (MSs) and spherical microcapsules (MCs) or elongated MCs containing a combination of ground bacterial cellulose (GBC) and SPI as the healing agent. Spray emulsification, combined with solvent evaporation technique, was used to prepare MCs and MSs. The technique resulted in two MC morphologies: one primarily consisting of a mixture of porous MSs and spherical MCs and the other consisting of elongated MCs with aspect ratios as high as 50, depending on the surfactant and GBC amount used. While porous MSs made the resin stronger, they did not contribute to self-healing since they could not retain the healant. Part of the GBC, added during MC preparation, got successfully encapsulated into MCs to form strong GBC/SPI composite healtant. Most of the remaining GBC stayed on MC surfaces and was seen to enhance the MC/resin interfacial adhesion which, in turn, contributed to increased self-healing efficiency. Overall results indicated that resins with 20 wt% elongated MCs exhibited self-healing efficiencies of about 45% in strength and 59% in toughness. The results suggest that the integration of GBC in the healant could also work in other resin systems to enhance their self-healing efficiencies.

The efficiency and mechanism of a new absorption enhancer, malic acid, for enhancing the oral bioavailability of docetaxel

This study investigated the efficiency and the related mechanisms of a new absorption enhancer, DL-malic acid (MA), on the oral bioavailability of docetaxel (DTX). Polyethylene glycol polycarbonate (PEG-PCL) modified liposomes (PLip) were prepared for DTX, and incorporated into the pH-sensitive microspheres (MS) with sustained release. MA decreased the transepithelial electrical resistance (TEER) across a Caco-2 cell monolayer by 20% and 57% after 2 and 3 h of co-incubation with DTX-PLip and the cells, respectively, indicating that MA could open tight junctions but not instantaneously. After long enough exposure (4 h) of MA to the small intestine of rats, only the absorption rate constant (ka ) of DTX-PLip, but not Duopafei®, was increased, which could be related to the intestinal mucosal permeability of DTX. After co-administration in rats, MA significantly enhanced the oral bioavailability of DTX in DTX-PLip-MS from 44.67% to 81.27%, rather than DTX-PLip and Duopafei®, which could be related to the prolonged intestinal retention time of DTX-PLip via the MS and the promoted drug intercellular transport by MA. The absorption-enhancing effects of MA on DTX-PLip-MS were further confirmed by in vivo imaging. The above findings suggest that MA served as a new and efficient absorption enhancer for DTX-PLip-MS. HIGHlIGHTS In this study, malic acid as a new absorption enhancer for DTX in polymer-liposome (PLip) embedded in pH-sensitive microspheres (MS) was found for the first time. The malic acid could significantly enhance oral bioavailability of DTX in DTX-PLip-MS (from 44.67 % to 81.27%) rather than Duopafei® and DTX-PLip after co-administration. The absorption enhancement may be closely related to the intestinal retention time and mucosal permeability. These findings will provide an important reference for the study of absorption enhancers for promoting intercellular insoluble drug transport.

Study on Magnetic Porous Carbon Microspheres as a Novel Adsorbent for Malachite Green

AbstractIn this paper, a novel adsorbent of magnetic mesoporous carbon microspheres (MCS) are prepared by template methods and using nano‐Fe3O4 particles as magnetic cores, and the adsorption capacity and mechanism are studied in detail. The results show that MCS exhibits high performance for removing malachite green (MG), the highest adsorption capacity can reach about 468.5 mg g−1. Furthermore, the Langmuir adsorption isotherm model and the quasi‐second‐order kinetic model can explain the experimental phenomena very well. And the high adsorption capacity of MCS is mainly attributed to its unique mesoporous structure by increasing the specific surface area and providing sufficient active sites. In addition, after magnetic separation and recovery, MCS can be regenerated with ethanol. And MCS maintains a high adsorption rate of 84.5 % after 5 cycles of MG adsorption and desorption. This composite material with high adsorption efficiency and rapid magnetic separation is a promising recyclable adsorbent for the actual wastewater treatment and purification process.

Design a novel multifunctional (CsPbBr3/Fe3O4)@MPSs@SiO2 magneto-optical microspheres for capturing circulating tumor cells

All inorganic lead halide perovskite nanocrystals with excellent photoelectric characteristics as one of attractive new photoelectric materials are capable to apply in a variety of optoelectronic devices, but their instability and toxicity strongly impedes biological application. Herein, a novel approach of combining physical loading with hydrolytic packaging was exploited to firstly implant CsPbBr3 nanocrystals (NCs) and Fe3O4 quantum dots (QDs) into the mesoporous polystyrene microspheres (MPSs), then a silica shell layer was further coated on it to form the stable, safe and non-toxic (CsPbBr3/Fe3O4)@MPSs@SiO2 magneto-optical microspheres. The double core-shells packaging way not only improves the stability of the magneto-optical microspheres, but also avoids direct contact between CsPbBr3 NCs and biological target such as circulating tumor cells (CTCs) to solve the problem of heavy metal Pb in such material system. These magneto-optical microspheres can capture CTCs from both breast cancer cells (MCF-7) and lung cancer patient's blood in a few minutes. This work created a simple, safe and one-step method to identify and capture CTCs, which opens a new chapter for the application of lead halide perovskite in the biological field.

Mucoadhesive gastroretentive microparticulate system for programmed delivery of famotidine and clarithromycin

Aim The present research was aimed to develop thiolated polyacrylic acid (TPA) based microspheres (MSPs) containing famotidine (FX) and clarithromycin (CLX). Methods TPA was synthesised from polyacrylic acid and l-cysteine in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC). The prepared TPA was characterised using FT-IR (Fourier transform-infra red), 1H-NMR (proton nuclear magnetic resonance) spectroscopy, P-XRD (powder X ray diffraction) method, and zeta potential. The analytical tools have supported the formation of TPA. The thiolated microspheres were prepared by emulsion solvent evaporation method using 0.75% w/v polymer concentration and stirring at 400 rpm for 8 hr. Results The average particle size and zeta potential of optimised formulation was found to be 25.2 ± 1.87 μm and –26.68 mV, respectively. The entrapment efficiency of the optimised formulation was obtained 67.20% for FX and 70.20% for CLX. The developed microspheres were swelled only in 4 h from 0.5 to 0.9. The in vitro mucoadhesive study and in vitro drug release studies demonstrated that microspheres showed mucoadhesive property. In in vitro drug release studies, the release of FX and CLX were observed to be 58.68% and 60.48%, respectively from microspheres in 8 h. The thiolated microspheres showed higher adhesion time (7.0 ± 0.8 h) in comparison to the plain microspheres (2.6 ± 0.4 h). Conclusion The prepared TPA based mucoadhesive microspheres can be utilised as carriers for the treatment of peptic ulcer caused by Helicobacter pylori which will offer enhanced residence time for the rational drug combination in the gastric region.

Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening complication of pulmonary embolism. As existing animal models of CTEPH do not fully recapitulate complex disease pathophysiology, we report a new rat model for CTEPH evoked by repetitive embolization of the distal pulmonary artery branches with partially biodegradable alginate microspheres (MSs). MSs (180 ± 28 μm) were intravenously administered eight times at 4-day intervals; control animals received saline. The validity of the model was confirmed using transthoracic echocardiography, exercise testing, catheterization of the right ventricle, and histological examination of the lung and heart. The animals in the CTEPH group demonstrated a stable increase in right ventricular systolic pressure (RVSP) and decreased exercise tolerance. Histopathological examination revealed advanced medial hypertrophy in the small pulmonary arteries associated with fibrosis. The diameter of the main pulmonary artery was significantly larger in the CTEPH group than in the control group. Marinobufagenin and endothelin-1 serum levels were significantly elevated in rats with CTEPH. In conclusion, repetitive administration of alginate MSs in rats resulted in CTEPH development characterized by specific lung vasculature remodeling, reduced exercise tolerance, and a persistent rise in RVSP. The developed model can be used for pre-clinical testing of promising drug candidates.

PLGA/PCADK composite microspheres containing hyaluronic acid–chitosan siRNA nanoparticles: A rational design for rheumatoid arthritis therapy

Myeloid cell leukemia-1 (Mcl-1), a member of the Bcl-2 anti-apoptotic family, is overexpressed in the synovial macrophages of patients with rheumatoid arthritis (RA). Small interfering RNA (siRNA) Mcl-1 can induce macrophage apoptosis in the joints and is a potential therapeutic target of RA. Nevertheless, the application of siRNA is limited owing to its instability and susceptibility to degradation in vivo. To address these shortcomings, we developed composite microspheres (MPs) loaded with hyaluronic acid (HA)–chitosan (CS) nanoparticles (NPs). First, we synthesized HA–CS/siRNA NPs (HCNPs) using ionotropic gelation process. Then, HCNPs, as an internal aqueous phase, were loaded into poly (D, L-lactide-co-glycolide) (PLGA) and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) MPs using the double emulsion method. The NPs-in-MPs (NiMPs) composite system provided sustained release of NPs, protected siRNA against nuclease degradation in the serum, and could readily cross the cellular membrane. In addition, we evaluated the advantages of NiMPs in an adjuvant-induced arthritis rat model. Our experimental results demonstrate that NiMPs have greater pharmacodynamic effects than common MPs. Meanwhile, compared with HCNPs, NiMPs reduced the frequency of drug administration. Therefore, NiMPs are a promising and novel siRNA delivery vehicle for RA therapy.

Recent progress and challenges for polymeric microsphere compared to nanosphere drug release systems: Is there a real difference?

Polymeric microspheres (MSs) and nanospheres (NSs) composed of synthetic and natural polymers can encapsulate anticancer drugs, among other therapeutics, acting as drug carriers to release them at controlled rates over long periods of time. These carriers present several potential advantages including simple preparation methods, suitable control over the sustained release of medications or stem cells, triggered release resulting from stimulus-responsive delivery, improved physical properties such as porosity and stable scaffolds for tissue engineering, and possible applications as microreactors and nanoreactors compared to conventional drug delivery systems. Moreover, many of these factors can impact drug release rates by polymeric MSs and NSs. Herein, drug delivery systems based on polymeric MSs and NSs are described and compared according to recent advances and challenges, and poignant thoughts on what the field needs to progress are presented.

Hydrogel microspheres for spatiotemporally controlled delivery of RNA and silencing gene expression within scaffold-free tissue engineered constructs

Delivery systems for controlled release of RNA interference (RNAi) molecules, including small interfering (siRNA) and microRNA (miRNA), have the potential to direct stem cell differentiation for regenerative musculoskeletal applications. To date, localized RNA delivery platforms in this area have focused predominantly on bulk scaffold-based approaches, which can interfere with cell-cell interactions important for recapitulating some native musculoskeletal developmental and healing processes in tissue regeneration strategies. In contrast, scaffold-free, high density human mesenchymal stem cell (hMSC) aggregates may provide an avenue for creating a more biomimetic microenvironment. Here, photocrosslinkable dextran microspheres (MS) encapsulating siRNA-micelles were prepared via an aqueous emulsion method and incorporated within hMSC aggregates for localized and sustained delivery of bioactive siRNA. siRNA-micelles released from MS in a sustained fashion over the course of 28 days, and the released siRNA retained its ability to transfect cells for gene silencing. Incorporation of fluorescently labeled siRNA (siGLO)-laden MS within hMSC aggregates exhibited tunable siGLO delivery and uptake by stem cells. Incorporation of MS loaded with siRNA targeting green fluorescent protein (siGFP) within GFP-hMSC aggregates provided sustained presentation of siGFP within the constructs and prolonged GFP silencing for up to 15 days. This platform system enables sustained gene silencing within stem cell aggregates and thus shows great potential in tissue regeneration applications. Statement of SignificanceThis work presents a new strategy to deliver RNA-nanocomplexes from photocrosslinked dextran microspheres for tunable presentation of bioactive RNA. These microspheres were embedded within scaffold-free, human mesenchymal stem cell (hMSC) aggregates for sustained gene silencing within three-dimensional cell constructs while maintaining cell viability. Unlike exogenous delivery of RNA within culture medium that suffers from diffusion limitations and potential need for repeated transfections, this strategy provides local and sustained RNA presentation from the microspheres to cells in the constructs. This system has the potential to inhibit translation of hMSC differentiation antagonists and drive hMSC differentiation toward desired specific lineages, and is an important step in the engineering of high-density stem cell systems with incorporated instructive genetic cues for application in tissue regeneration.

Electrical percolation in extrinsically conducting, poly(\u03b5-decalactone) composite neural interface materials

By providing a bidirectional communication channel between neural tissues and a biomedical device, it is envisaged that neural interfaces will be fundamental in the future diagnosis and treatment of neurological disorders. Due to the mechanical mismatch between neural tissue and metallic neural electrodes, soft electrically conducting materials are of great benefit in promoting chronic device functionality. In this study, carbon nanotubes (CNT), silver nanowires (AgNW) and poly(hydroxymethyl 3,4-ethylenedioxythiophene) microspheres (MSP) were employed as conducting fillers within a poly(ε-decalactone) (EDL) matrix, to form a soft and electrically conducting composite. The effect of a filler type on the electrical percolation threshold, and composite biocompatibility was investigated in vitro. EDL-based composites exhibited favourable electrochemical characteristics: EDL/CNT—the lowest film resistance (1.2 ± 0.3 kΩ), EDL/AgNW—the highest charge storage capacity (10.7 ± 0.3 mC cm− 2), and EDL/MSP—the highest interphase capacitance (1478.4 ± 92.4 µF cm−2). All investigated composite surfaces were found to be biocompatible, and to reduce the presence of reactive astrocytes relative to control electrodes. The results of this work clearly demonstrated the ability of high aspect ratio structures to form an extended percolation network within a polyester matrix, resulting in the formulation of composites with advantageous mechanical, electrochemical and biocompatibility properties.

Immobilized thrombin on X-ray radiopaque polyvinyl alcohol/chitosan embolic microspheres for precise localization and topical blood coagulation

Trans-catheter arterial embolization (TAE) plays an important role in treating various diseases. The available embolic agents lack X-ray visibility and do not prevent the reflux phenomenon, thus hindering their application for TAE therapy. Herein, we aim to develop a multifunctional embolic agent that combines the X-ray radiopacity with local procoagulant activity. The barium sulfate nanoparticles (BaSO4 NPs) were synthesized and loaded into the polyvinyl alcohol/chitosan (PVA/CS) to prepare the radiopaque BaSO4/PVA/CS microspheres (MS). Thereafter, thrombin was immobilized onto the BaSO4/PVA/CS MS to obtain the thrombin@BaSO4/PVA/CS MS. The prepared BaSO4/PVA/CS MS were highly spherical with diameters ranging from 100 to 300 μm. In vitro CT imaging showed increased X-ray visibility of BaSO4/PVA/CS MS with the increased content of BaSO4 NPs in the PVA/CS MS. The biocompatibility assessments demonstrated that the MS were non-cytotoxic and possessed permissible hemolysis rate. The biofunctionalized thrombin@BaSO4/PVA/CS MS showed improved hemostatic capacity and facilitated hemostasis in vitro. Additionally, in vivo study performed on a rabbit ear embolization model confirmed the excellent X-ray radiopaque stability of the BaSO4/PVA/CS MS. Moreover, both the BaSO4/PVA/CS and thrombin@BaSO4/PVA/CS MS achieved superior embolization effects with progressive ischemic necrosis on the ear tissue and induced prominent ultrastructural changes in the endothelial cells. The findings of this study suggest that the developed MS could act as a radiopaque and hemostatic embolic agent to improve the embolization efficiency.

A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies.

We assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult retinal pigment epithelial cell-line-19 (ARPE-19) cells, primate choroidal endothelial (RF/6A) cells, and the survival of isolated mouse retinal ganglion cells (RGCs). The morphology of the MSs, particle size, and encapsulation efficiencies of the active substances were evaluated. In vitro release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability, terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labelling (TUNEL) apoptosis, functional wound healing migration (ARPE-19; migration), and (RF/6A; angiogenesis) assays were conducted. The safety of MS intravitreal injection was assessed using hematoxylin and eosin, neuronal nuclei (NeuN) immunolabeling, and TUNEL assays, and RGC in vitro survival was analyzed. MSs delivered GDNF and co-delivered GDNF/BDNF in a sustained manner over 77 days. The BDNF/GDNF combination increased RPE cell migration, whereas no effect was observed on RF/6A. MSs did not alter cell viability, apoptosis was absent in vitro, and RGCs survived in vitro for seven weeks. In mice, retinal toxicity and apoptosis was absent in histologic sections. This delivery strategy could be useful as a potential co-therapy in retinal degenerations and glaucoma, in line with future personalized long-term intravitreal treatment as different amounts (doses) of microparticles can be administered according to patients’ needs.

Serially pH-Modulated Hydrogels Based on Boronate Ester and Polydopamine Linkages for Local Cancer Therapy.

Elaborately and serially pH-modulated hydrogels possessing optimized viscoelastic natures for short gelation time and single syringe injection were designed for peritumoral injection of an anticancer agent. Boronate ester bonds between phenylboronic acid (PBA) (installed in HA-PBA (HP)) and dopamine (included in HA-dopamine (HD)) along with self-polymerization of dopamine (via interactions between HD conjugates) were introduced as the main cross-linking strategies of a hyaluronic acid (HA) hydrogel. Considering pKa values (8.0-9.5) of PBA and dopamine, the pH of each polymer dispersion was controlled elaborately for injection through a single syringe, and the final pH was tuned nearby the physiological pH (pH 7.8). The shear-thinning behavior, self-healing property, and single syringe injectability of a designed hydrogel cross-linked nearby physiological pH may provide its convenient application to peritumoral injection and prolonged retention in local cancer therapy. Erlotinib (ERT) was encapsulated in a microsphere (MS), and it was further embedded in an HP/HD-based hydrogel for sustained and locoregional delivery. A rheologically tuned hydrogel containing an ERT MS exhibited superior tumor-suppressive efficiencies compared to the other groups in A549 tumor-bearing mice. A designed injectable hydrogel through a single syringe system may be efficiently applied to local cancer therapy with lower toxicities to healthy organs.

Impact of the physico-chemical properties of polymeric microspheres functionalized with cell adhesion molecules on the behavior of mesenchymal stromal cells

Polymeric, biodegradable, microspheres (MS) presenting a biomimetic surface of extracellular matrix (ECM) proteins are currently used for transporting cells and/or encapsulated proteins for regenerative medicine studies. They can be made of (lactic-co-glycolic acid) (PLGA) or of a more hydrophilic PLGA-P188 (Poloxamer188)-PLGA polymer allowing for the complete release of the therapeutic proteins. They promote stem cell adhesion, cell survival and differentiation after transplantation. Although the biological effectiveness of these microcarriers is established, a detailed understanding of the protein and cell interactions with the microcarrier surface remain unclear due to a lack of information of their surface properties. The aim of this study was to characterize the physicochemical properties of two polymeric MS systems and determine the effect of laminin and poly-d-lysine coated microcarriers on stem cell adhesion, survival and neuronal differentiation. The hydrophobicity and topography of PLGA MS promoted protein adsorption and the stem cells quickly adhered and spread on the surface of these microcarriers. In contrast less proteins adsorbed onto PLGA-P188-PLGA MS and although cells adhered to these microcarriers, they remained round and did not spread on their surface. Despite these early-stage differences, our results suggest that the nature of the MS does not strongly influence the long-term cell behavior. The cells exhibit the same cell number, differentiation profile and ability to secrete ECM molecules regardless of the type of microcarrier used. Likely the ECM molecules that form a microenvironment around both of these 3D microcarrier/cell constructs over time play a role in this converging cell behavior. We have thus furthered our understanding of the physicochemical properties of polymeric cell carriers affecting stem cell behavior to help tailor suitable microcarriers for neuroregenerative applications.

Highly Open Porous Gelatin Microspheres with MC3T3-E1 Cells for the Repair of Skull Defect

To address nondegradable or slowly degradable scaffolds for open skull surgery, microspheres (MSs)-based cell scaffolds have been used to repair skull defects. However, most MSs-based cell scaffolds show poor cell adherence, differentiation and tissue infiltration. Consequently, gelatin, a macromolecular hydrophilic colloid, has been employed to prepare highly open porous microspheres with particle sizes of 100–300 µm. Highly open porous gelatin microspheres (HOPG-MSs) have 2–70 µm of open pores and interconnected paths. HOPG-MSs has the advantage of MSs and scaffolds, and could be used as a carrier for osteoblast transplantation. In addition to convenient transplantation into defective tissue and in contrast to the poor performances of covalently crosslinked gelatin microspheres (CCG-MSs) and open porous gelatin/hydroxyapatite composite microspheres (HA-OPG-MSs), HOPG-MSs present suitable surface pores and interconnected passages, thereby promoting cell adhesion and cell proliferation in vitro, and improving the differentiation of mouse embryonic osteoblast precursor cells (MC3T3-E1 cells). HOPG-MSs also greatly promote osteoblast regeneration compared with traditional CCG-MSs and HA-OPG-MSs in ectopic bone formation mouse models. HOPG-MSs can not only absorb nutrients from outside the scaffold but also protect cells during transplantation so that more live cells are allowed to proliferate and migrate to the damaged tissue. The results of this study suggest that cell-laden HOPG-MSs scaffolds can promote bone growth and integration, laying a foundation for further research on the reconstruction of skull defects. Funding: This work was supported by the National Natural Science Foundation of China, China (Grant No. 21604045, 81671305 and 81470059), the Natural Science Foundation of Shandong Province, China (Grant No. ZR2016BQ36), the Applied Basic Research Program of Qingdao, China (Grant No. 16-5-1-91-jch). Declaration of Interest: None to declare. Ethical Approval: The in vivo study was approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University, and under its guidance, all animal experiments were carried out.

Novel optimized drug delivery systems for enhancing spinal cord injury repair in rats

Effective and accurate delivery of drugs to tissue with spinal cord injury (SCI) is the key to rehabilitating neurological deficits. Sustained-release microspheres (MS) have excellent degradability and can aid in the long-term release of drugs. However, the burst release phenomenon can cause unexpected side effects. Herein, we developed and optimized an injectable poly(lactic-co-glycolic acid) (PLGA) MS loaded with melatonin(Mel), which were mixed further with Laponite hydrogels (Lap/MS@Mel, a micro-gel compound) in order to reduce the burst release of MS. Thus, these MS were able to achieve stable and prolonged Mel release, as well as synergistic Lap hydrogel in order to repair neural function in SCI by in situ injection. In clinical practice, patients with SCI have complicated conditions and significant inter-individual differences, which means that a single route of administration does not meet actual clinical needs. Thus, the nanospheres are synthesized and subsequently coated with platelet membrane (PM) in order to form PM/MS@Mel (nano-PM compound) for sustained and precision-targeted delivery of Mel intravenously in the SCI. Notably, optimized microsphere delivery systems have improved Mel regulation polarization of spinal microglial/macrophages, which can reduce loss of biomaterials due to macrophage-induced immune response during implantation of spinal cord tissue. These two new delivery systems that are based on MS provide references for the clinical treatment of SCI, according to different requirements.

Hybrid natural hydrogels integrated with voriconazole-loaded microspheres for ocular antifungal applications.

Fungal keratitis is a major threat to ocular morbidity and blindness. The therapeutic efficacy of eye drops against fungal keratitis is limited by their poor bioavailability, especially in patients with corneal stromal ulcers that lead to tissue defects. Therefore, intervention measures that can control fungal infection while promoting tissue regeneration are desirable. Herein, we designed and fabricated natural antifungal hydrogels that comprise a decellularized porcine cornea (DPC), gelatin and microspheres (MCs) containing voriconazole (Vor) for the management of fungal keratitis with focal corneal stromal defects. The size and structure of the Vor-loaded MCs were characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The antifungal drug Vor showed that continuous release from the hybrid hydrogel system for up to 7 days and that MCs loading did not affect the mechanical properties, in vitro release profile or cytocompatibility of the hybrid hydrogel. Moreover, the Vor-loaded hydrogels exhibited excellent antifungal properties against F. solani and A. fumigatus. The efficiency of the natural antifungal hydrogel was evaluated by an ex vivo infectious rabbit corneal defect model. After 24 h, the number of fungal colony-forming units (CFU) significantly decreased in antifungal hydrogel-treated corneal tissue compared with that in non-treated corneas and corneas treated with hydrogels without Vor. The above results demonstrated that this natural hydrogel-based drug delivery system holds great promise for preventing fungal keratitis infection while promoting focal corneal stromal regeneration. Additionally, natural hybrid hydrogels might be a candidate material for use with various drugs in the effective treatment of many other ocular diseases.

Ultra-durable superhydrophobic surfaces from 3D self-similar network via co-spraying of polymer microspheres and nanoparticles

Establishing mechanically durable superhydrophobic (SH) surface using adhesive polymer and nanoparticles (NPs) is an effective, scalable and simple approach, however, the optimizing 3D coupling of two components is highly challenging. Herein, a novel approach involving co-spraying of polystyrene (PS) microspheres (MPs) and perfluorinated chained nanoparticles (F-CNPs) and subsequent hot-press is reported. An optimal configuration of self-similar 3D network is established, in which adhesive polymer and decorated nanoparticles are fully utilized. Hence, our coating remains superhydrophobicity even after 1200 cm unidirectional abrasion under 10 kPa. More impressively, the superhydrophobicity could be maintained even after 14 h of water jetting impact (~25 kPa) or 230 cycles of freeze-thaw cycles. We believe our network design of full utilizing adhesive polymer and superhydrophobic particles enhances the potential applications of durable superhydrophobic surfaces in various harsh environments.