Integrity Of Capsules Research Articles

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

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

A new Critically Endangered species of stone breaker (Phyllanthus, Phyllanthaceae) from Central Brazil, with notes on its leaf and stem anatomy

A new species from the state of Goiás, Brazil, Phyllanthus pterocaulis, is described and illustrated, with comments on its geographic distribution and environmental preferences, phenology, morphological relationships, and systematic position. It is morphologically allied with Phyllanthus avicularis, P. heliotropus, and P. hyssopifolioides, but differs from all of them by a set of characters related to cymules sex, presence and types of trichomes on leaves and stems, leaf consistency, numbers of sepals in flower of both sexes, integrity of stamens, capsules and seeds. Additionally, we provide images of the new species in the field, conservation status, mapped distribution, the anatomical description of its stem and leaves, and a key to differentiate it from the other similar species belonging to Phyllanthus sect. Loxopodium occurring in Brazil. The new species is one of the few in the genus that occurs in shaded environments in seasonal dry forests within the Cerrado biome.

Coaxial Alginate Hydrogels: From Self-Assembled 3D Cellular Constructs to Long-Term Storage.

Alginate as a versatile naturally occurring biomaterial has found widespread use in the biomedical field due to its unique features such as biocompatibility and biodegradability. The ability of its semipermeable hydrogels to provide a favourable microenvironment for clinically relevant cells made alginate encapsulation a leading technology for immunoisolation, 3D culture, cryopreservation as well as cell and drug delivery. The aim of this work is the evaluation of structural properties and swelling behaviour of the core-shell capsules for the encapsulation of multipotent stromal cells (MSCs), their 3D culture and cryopreservation using slow freezing. The cells were encapsulated in core-shell capsules using coaxial electrospraying, cultured for 35 days and cryopreserved. Cell viability, metabolic activity and cell–cell interactions were analysed. Cryopreservation of MSCs-laden core-shell capsules was performed according to parameters pre-selected on cell-free capsules. The results suggest that core-shell capsules produced from the low viscosity high-G alginate are superior to high-M ones in terms of stability during in vitro culture, as well as to solid beads in terms of promoting formation of viable self-assembled cellular structures and maintenance of MSCs functionality on a long-term basis. The application of 0.3 M sucrose demonstrated a beneficial effect on the integrity of capsules and viability of formed 3D cell assemblies, as compared to 10% dimethyl sulfoxide (DMSO) alone. The proposed workflow from the preparation of core-shell capsules with self-assembled cellular structures to the cryopreservation appears to be a promising strategy for their off-the-shelf availability.

Corrosion behavior of aluminum alloy 5754 in cement‐based matrix‐simulating nuclear waste disposal conditions

AbstractDepending on the lifetime and level of radioactivity of radioactive wastes, different disposal facilities are considered. Though low‐ and intermediate‐level short‐lived waste can be disposed in surface disposal facilities, deep geological disposal is considered for high‐ and intermediate‐level long‐lived waste. In France and Belgium, long‐term disposal is studied in clay host rock media. For aluminum, the disposal concept is based on encapsulation of the waste in a cement‐based matrix. It is also well‐known that aluminum is prone to severe corrosion in sufficiently alkaline environments leading to possible hydrogen production. To ensure the safety of the disposal facilities and the integrity of the cement capsules, the amount of aluminum that is disposed in each waste package must be specified and is limited to mitigate the level of hydrogen production by aluminum corrosion. In the present study, the corrosion resistance of an aluminum alloy (grade EN‐AW‐5754/H111) in two different cement matrices was studied in different configurations at room temperature. In each case, the evolution of hydrogen production was monitored to address the corrosion rate variation versus time.

Fe-functionalized paramagnetic sporopollenin from pollen grains: one-pot synthesis using ionic liquids

The preparation of Fe-decorated sporopollenins was achieved using pollen grains and an ionic liquid as solvent and functionalizing agent. The integrity of the organic capsules was ascertained through scanning electron microscopy studies. The presence of Fe in the capsule was investigated using FT-IR, X-ray photoemission spectroscopy and energy-dispersive X-ray spectroscopy. Electron paramagnetic resonance and magnetization measurements allowed us to demonstrate the paramagnetic behavior of our Fe-functionalized sporopollenin. A few potential applications of pollen-based systems functionalized with magnetic metal ions via ionic liquids are discussed.

Injectable biodegradable bi-layered capsule for sustained delivery of bevacizumab in treating wet age-related macular degeneration

Vascular endothelial growth factor (VEGF) is a key regulator of abnormal blood vessel growth. As such, bevacizumab-based inhibition of VEGF has been the clinically adopted strategy to treat colorectal and breast cancers as well as age-related macular degeneration (AMD). However, as the treatment of vascular diseases often requires a high drug concentration for a long period, the burst release of bevacizumab remains a critical limitation in anti-VEGF-based therapies. Maintaining bevacizumab at high concentrations over extended periods remains challenging due to insufficient drug loading capacity and drug-device interactions. We report the development of a polymeric based bi-layered capsule that could address these challenges by extending the release over one year, thereby providing an effective platform enabling treatment of chronic vascular diseases. Remarkably, the developed capsules have a bi-layered structure which ensures the structural integrity of the injectable capsules and appropriate diffusion of bevacizumab by providing optimal physical trapping and electrostatic interaction. Meanwhile, the central hollow design enables a higher drug loading to meet the need for long-term release of bevacizumab for several months to one year. Using an in vitro drug release assay, we demonstrated that the bi-layered capsule could produce longer-term local drug administration by intravitreal injection compared to previously reported devices. The capsules also present minimal toxicity and maintain anti-VEGF potency, suggesting that our approach may have the potential to treat vascular-related diseases using bevacizumab.

Renal Protective Effects of Low Molecular Weight of Inonotus obliquus Polysaccharide (LIOP) on HFD/STZ-Induced Nephropathy in Mice.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in diabetes mellitus. Oxidative stress, insulin resistance and pro-inflammatory cytokines have been shown to play an important role in pathogeneses of renal damage on type 2 diabetes mellitus (DM). Inonotus obliquus (IO) is a white rot fungus that belongs to the family Hymenochaetaceae; it has been used as an edible mushroom and exhibits many biological activities including anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic properties. Especially the water-soluble Inonotus obliquus polysaccharides (IOPs) have been previously reported to significantly inhibit LPS-induced inflammatory cytokines in mice and protect from streptozotocin (STZ)-induced diabetic rats. In order to identify the nephroprotective effects of low molecular weight of IOP fraction (LIOP), from the fruiting bodies of Inonotus obliquus, high-fat diet (HFD) plus STZ-induced type 2-like diabetic nephropathy C57BL/6 mice were investigated in this study. Our data showed that eight weeks of administration of 10–100 kDa, LIOP (300 mg/kg) had progressively increased their sensitivity to glucose (less insulin tolerance), reduced triglyceride levels, elevated the HDL/LDL ratio and decreased urinary albumin/creatinine ratio(ACR) compared to the control group. By pathological and immunohistochemical examinations, it was indicated that LIOP can restore the integrity of the glomerular capsules and increase the numbers of glomerular mesangial cells, associated with decreased expression of TGF-β on renal cortex in mice. Consistently, three days of LIOP (100 μg/mL) incubation also provided protection against STZ + AGEs-induced glucotoxicity in renal tubular cells (LLC-PK1), while the levels of NF-κB and TGF-β expression significantly decreased in a dose-dependent manner. Our findings demonstrate that LIOP treatment could ameliorate glucolipotoxicity-induced renal fibrosis, possibly partly via the inhibition of NF-κB/TGF-β1 signaling pathway in diabetic nephropathy mice.

Improving the survivability of Nb-encapsulated Ga targets for the production of 68Ge

At the Los Alamos Neutron Science Center (LANSCE) Isotope Production Facility (IPF), radioisotopes are produced for medical, scientific, and industrial applications by irradiating various targets with a 100MeV, 230μA proton beam. The medical isotope germanium-68 is produced by irradiating Nb capsules containing molten Ga target material. During irradiation, the Nb is subjected to intense radiation damage, corrosive attack by Ga, and mechanical and thermally-induced stresses for an extended period. Maintaining the structural integrity of the Nb target capsules during irradiation is crucial to contain the molten Ga target and the radioisotope product. In the present work, we focus on potential material related factors and assess the effect of the Nb stock material on target durability. We do so by comparing post-irradiation target mortality information to data collected during pre-irradiation ultrasound testing and X-ray imaging. We also explore possible failure mechanisms by using MCNP6 simulations and ANSYS codes to predict the induced atom displacement levels, hydrogen gas built-up, temperature distribution, and mechanical stresses. Our analysis, performed entirely in the context of an aggressive production program that allows for only limited diagnostic interference, suggests that using Nb stock with reasonably large and uniform grains is the most important factor in reducing early target failure at integrated beam current values <18mAh and random failure at the face of the rear window at <60mAh. We discuss possible failure mechanisms of failed targets that were fabricated using the same stock material and grain structure and then irradiated to integrated beam current values of up to 60mAh and more. Based on these observations, we have enacted new specifications for Nb stock material quality, target design, and limits on integrated beam current. These changes have resulted in improved Nb capsule survivability.

Sequential Damage Assessment of the Different Components of the Posterior Ligamentous Complex After Magnetic Resonance Imaging Interpretation

Prospective cohort study. To study whether there is a sequential pattern in the posterior ligamentous complex (PLC) rupture caused by deforming traumatic forces by analyzing magnetic resonance (MR) images in a consecutive prospective cohort of patients with traumatic vertebral fracture. PLC plays an important role in vertebral stability. However, the sequence in which the different components of the PLC tear, in the face of traumatic forces, has not been yet described. Prospective study of 74 consecutive vertebral acute traumatic fractures analyzed using radiography and magnetic resonance imaging (MRI) (FS-T2-w/short-tau inversion-recovery [STIR] sequences). Fracture morphology was classified according to the AO classification. Integrity of each PLC component-facet capsules, interspinous ligament (ISL), supraspinous ligament (SSL), and ligamentum flavum (LF)-was assessed and classified as intact, edema, or disruption. ISL edema was further subdivided depending on the extension (>50%/<50%). We analyzed the association between MRI signal and the AO progressive scale of morphological damage. AO type A1/A2 fractures associated with only facet distraction. A3 fractures showed additional ISL edema, usually less than 50%, with neither SSL nor LF disruption. Type B1 fractures associated with facet distraction, ISL edema or disruption, and low rate of SSL/LF disruptions; B2 fractures increased SS/LF disruption rates. Type C fractures associated with facet fracture or dislocation and ISL, SSL, or LF complete rupture. We found high association (P < 0.001) between AO progressive scale and MRI signal. MRI analysis showed that posterior distraction forces begin in the facets and extend throughout the ISL, starting at its posterosuperior margin (finally disinserting the SSL superiorly) and traveling diagonally toward anteroinferior border, finally tearing the LF. MR images correlated with AO progressive scale of morphological damage, which showed a progressive orderly rupture sequence among the different PLC components as traumatic forces increased.

Biomechanical Comparison of Anterior, Posterior, and Circumferential Fixation After One-Level Anterior Cervical Corpectomy in the Human Cadaveric Spine

In vitro biomechanical study of cadaveric cervical spine. To compare the rigidity of the cervical spine after anterior, posterior, and circumferential fixation after 1-level corpectomy, and evaluate the effects of the integrity of the facet capsules and posterior ligaments (PL). Anterior cervical corpectomy is commonly used for decompression of the spinal canal in the treatment of different pathologic conditions. The effect of the integrity of the facet capsules and PLs on the biomechanical stability provided by anterior, posterior, or circumferential fixation following 1-level corpectomy has not been investigated. Nine cadaveric cervical spines were potted rostrally at C2, and caudally at T1-T2, and were tested in 6 directions with pure moment application, in 5 conditions: In the intact spine, after a C5 corpectomy and anterior fixation, after anterior fixation and disruption of the C4-C5 and C5-C6 facet capsules and PL, after circumferential fixation, and after posterior fixation alone without anterior cage. Angular motion of C4 relative to C6 was measured. Despite C5 corpectomy, anterior grafting and plate fixation was more rigid than the intact spine with all loads in flexion, at loads of 0.5 Nm and 1.0 Nm in right axial rotation and right lateral bending, and at all loads in left lateral bending. Posterior ligamentous disruption increased motion in the coronal and axial planes, but not in the sagittal plane. Circumferential instrumentation resulted in a significant reduction in motion of the spine compared with anterior instrumentation in both the coronal and axial planes but not in the sagittal plane. Posterior fixation without anterior cage failed to limit cervical spine motion in the sagittal plane, but was restrictive in axial rotation and lateral bending when compared with circumferential fixation. After C5 corpectomy, with intact PLs and facet capsules, anterior instrumentation is sufficient for spinal stabilization as the resultant construct is more rigid than the intact state. In the presence of C5 corpectomy with PL and bilateral facet capsule disruption, anterior plus posterior instrumentation is more rigid than anterior instrumentation alone in the axial and coronal planes and more rigid than posterior instrumentation without anterior cage in the sagittal plane.

Physical stability and resistance to peroxidation of a range of liquid-fill hard gelatin capsule products on extreme long-term storage

Background: The industrial take-up of liquid-fill hard capsule technology is limited in part by lack of published long-term physical and chemical stability data which demonstrate the robustness of the system.Objective: To assess the effects of extreme long-term storage on liquid-fill capsule product quality and integrity, with respect to both the capsules per se and a standard blister-pack type (foil–film blister).Materials and methods: Fourteen sets of stored peroxidation-sensitive liquid-fill hard gelatin capsule product samples, originating ~20 years from the current study, were examined with respect to physical and selected chemical properties, together with microbiological evaluation.Results and discussion: All sets retained physical integrity of capsules and blister-packs. Capsules were free of leaks, gelatin cross-linking, and microbiological growth. Eight samples met a limit (anisidine value, 20) commonly used as an index of peroxidation for lipid-based products with shelf lives of 2–3 years. Foil–film blister-packs using PVC or PVC–PVdC as the thermoforming film were well-suited packaging components for the liquid-fill capsule format.Conclusion: The study confirms the long-term physical robustness of the liquid-fill hard capsule format, together with its manufacturing and banding processes. It also indicates that various peroxidation-sensitive products using the capsule format may be maintained satisfactorily over very prolonged storage periods.

Assessment of X-ray tomography for irradiated IFMIF/HFTM RIG

An inspection procedure to assess the mechanical integrity of IFMIF capsules and rigs during the irradiation campaign is necessary. In a number of experiments, we previously proved that X-ray tomography is a reliable solution for official inspections of the structural integrity of IFMIF complete assemblies before and after various tests (tensile, creep-fatigue, fracture toughness, crack growth, microstructure swelling). The next main challenge is to qualify the transmission microtomography inspection as a tool for non-destructive inspection during maintenance (beam-off) periods and after irradiation campaigns. The influence of the sample gamma radioactivity (produced by neutron activation during irradiation campaigns) on the tomographic reconstruction quality is investigated in this paper. The evaluation is performed for the specific configuration of newly manufactured IFMIF irradiation capsules. Experimental X-ray radiographic data together with simulated gamma radiographic images were considered. Latest activation data were incorporated. For the numerical simulations, a working environment able to provide a realistic numerical simulation was constructed on the basis of two well established Monte Carlo computer codes: SIMIND and ITS. The optimal parameters of the collimation system, essential for the investigation of the irradiated samples, were determined. It is proved that transmission tomography is practicable, providing good quality reconstruction which allows accurate geometrical measurements. The procedure developed for tomography of irradiated HFTM can be applied for the inspection of other irradiated structures for which X-ray tomography represents a non-destructive inspection technique (NDT).

PH-responsive protein microcapsules fabricated via glutaraldehyde mediated covalent layer-by-layer assembly

Bovine serum albumin (BSA) hollow microcapsules were fabricated through glutaraldehyde (GA) mediated covalent layer-by-layer assembly. The GA cross-linking of the adsorbed BSA on the colloidal particles enabled their surfaces to be covered by reactive aldehyde groups, which reacted with BSA molecules to result in another covalently linked layer. Repeating of this cycle could then yield particles coated with BSA multilayers. Hollow microcapsules well dispersed in water were obtained after core removal. The good integrity and morphology of the BSA capsules were confirmed and characterized by confocal laser scanning microscopy, scanning electron microscopy and scanning force microscopy. The obtained BSA microcapsules possess reversible pH response, i.e., the capsules are permeable to macromolecules below pH 4 or above pH 10, while impermeable in between. The mechanisms of permeability transition were discussed. Using this property, dextran, with a molecular weight of ~155 kDa, was successfully loaded.

Ultrasonically Induced Opening of Polyelectrolyte Microcontainers

The effect of ultrasonic treatments of different intensity and duration on the integrity and permeability of polyelectrolyte capsules was investigated both in poly(allylamine)/poly(styrene sulfonate) and Fe(3)O(4)/poly(allylamine)/poly(styrene sulfonate) polyelectrolyte capsules. Ultrasonic treatment of polyelectrolyte capsules induces the destruction of the polyelectrolyte shell and the release of the encapsulated material even at short (5 s) sonification times. The presence of magnetite nanoparticles significantly improves the efficiency of the ultrasonically stimulated release of the encapsulated compounds and enables magnetically controlled delivery to the desired site before ultrasonic treatment. Release of the encapsulated compound induced at ultrasonic power comparable to those of ultrasonic generators applied in medicine, demonstrating practical application of the ultrasonically triggered capsule opening in medicine.

Encapsulated hepatocellular carcinoma: CT-pathologic correlations

This study is a retrospective evaluation of the correlations between the presence and integrity of the capsule of nodular hepatocellular carcinomas (HCC) by dynamic CT and histopathology, with histopathologic evidence of tumor propagation to surrounding hepatic parenchyma. Dynamic CT scans of 75 nodular HCCs in 73 patients (61 men, 12 women; age range, 32-81; mean, 53) were evaluated regarding capsule visualization and integrity. Histopathologic findings of HCCs in resected specimens were correlated with the presence of a capsule, tumor invasion onto the capsule, and with the presence of microvascular emboli in the surrounding liver parenchyma. On histopathologic examination, capsules were present in 57 of 75 nodular HCCs; the capsules were invaded by tumor in 18 nodules and there were microvascular emboli around the nodular HCC in 49 cases. Capsule visualization by CT was correlated with the presence of capsule by histopathology (P<0.001). Disruption of capsule by CT was correlated with tumor invasion by histopathology (P=0.003) and with microvascular tumor emboli (P<0.001). The presence and structural integrity of HCC capsules on CT was closely correlated with the presence of capsule on histopathology and the absence of microvascular tumor emboli.

Influence of Shell Structure on Stability, Integrity, and Mesh Size of Polyelectrolyte Capsules: Mechanism and Strategy for Improved Preparation

Novel polyelectrolyte microcapsules are developed using alternating layer-by-layer (LBL) adsorption of oppositely charged polyelectrolytes onto charged templates followed by core removal. These capsules have a continuous wall with a hollow interior and exhibit tunable permeability, which can be utilized for both sustained release from the capsule and precipitation reactions from the bulk to the capsule interior. The purpose of this work is to understand core removal mechanism and elucidate the structure−property relationships governing capsule stability and yield, integrity, and mesh size. To this end, melamine formaldehyde (MF) templates with polyelectrolyte multilayers (PEMs) of poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) were investigated by confocal Raman microscopy, surface force microscopy, and confocal laser scanning microscopy. The capsule structure is dominated by two critical factors: the wall thickness and the core decomposition condition. After optimization of the c...

Active metal brazing for joining glass-ceramic to titanium?a study on silver enrichment

A hermetic encapsulation system for implantable telemetric electronic devices has been developed. It is based on the combination of a glass-ceramic material transparent to radio-frequency signals with commercially pure titanium. The materials were joined by active metal brazing, resulting in a multi-layer structure. The in vivo and in vitro behaviour of this metal-ceramic interface was studied. In vivo experiments consisted of subcutaneous implantation of capsules in piglets and pigs with different weights, while the in vitro tests consisted of electrochemical techniques aimed at characterizing the degradation behaviour of the interface. Electrochemical experiments were conducted at 37°C in a simulated physiological solution (Hank's Balanced Salt Solution; HBSS). Results show that a silver-rich phase was formed at the interface, both in living tissue and in HBSS. Chloride seems to have an important role in the reaction mechanism. The mechanical integrity of the capsules was not affected by this reaction under in vivo conditions.