Narrow Results

Microcapsules comprising alginate and hyaluronic acid that can be decomposed by radiation are under development. Previously, we observed that radiation efficiently decomposes microcapsules comprising alginate and hyaluronic acid in the ratio 2:1 by weight. In this study, Yttrium (Y) was added to these microcapsules to improve their decomposition by radiation.

Hyaluronic acid solutions (0.1% weight/volume) were mixed into 0.2% alginate solution, and carboplatin (0.2 mmol) was added; the resultant was used for capsule preparation. Capsules were prepared by spraying the material into mixtures of 4.34% CaCl₂ solution supplemented with Y at final concentrations from 0 to 1.0 × 10⁻²%.

These capsules were irradiated by a single dose of 0.5, 1.0, 1.5, or 2 Gy with ⁶⁰Co γ-rays. Immediately after irradiation, we observed the release of the core contents of the microcapsule using a micro Particle Induced X-ray Emission (PIXE) camera.

The mean diameter of the microcapsules was 37.3 ± 7.8 μm. Maximum content of radiation-induced release was observed for liquid-core microcapsules prepared by polymerization in a 4.34% CaCl₂ solution supplemented with 5.5 × 10⁻³% Y.

Potentiostatic two step anodizing of titanium utilized for preparation of self organized titania nanotubes arrays with diameter of 150 nm. Then the new alginate method has been applied for incorporation of NiO into the nanotubes. The prepared hybrid materials have been characterized by various methods including field emission scanning electron microscopy, X-ray diffractometry and cyclic voltammetry analyses. The X-ray diffraction patterns of samples were also studied by Rietveld's method. Results showed that the prepared electrode containing anatase, rutile and NiO phases with fraction of 70, 8, and 22%, respectively. It was found that by application of the new method, porous NiO uniformly coated on nanotubes surface and great enhancement of specific capacitance from 0.14 to 3.8 mF cm^-2 could be obtained. The prepared nanocomposites are promising materials for supercapacitance application and also for solar energy harvesting systems.

We presented a new approach to produce Chitosan–Glutaraldehyde–Chitosan–Alginate (CGCA) hollow fiber with the capability of cell capture and adhesion for vascular tissue engineering. The CGCA hollow fiber was generated by sacrificing the inner part of alginate/chitosan (A/C) solid fiber using sodium citrate, followed by glutaraldehyde (GA) cross-linking chitosan to form stable imine bonds on the fiber surface. Furthermore, human umbilical vein endothelial cells (HUVEC) were captured by the CGCA hollow fiber surface and adhesive as layer pattern with good viability and normal morphology. This strategy facilitated the lumen structure formation with good biocompatibility by biomaterials modification, providing a promising and facile technique for blood vessel regeneration in vitro and in vivo.

Microencapsulation of mesenchymal stem cells (MSC) in alginate facilitates cell delivery, localization and survival, and modulates inflammation in vivo. However, we found that delivery of the widely used ∼ 0.5mm diameter encapsulated MSC (eMSC) by intrathecal injection into spinal cord injury (SCI) rats was highly variable. Injections of smaller (∼ 0.2 mm) diameter eMSC into the lumbar spine were much more reproducible and they increased the anti-inflammatory macrophage response around the SCI site. We now report that injection of small eMSC $>2$cm caudal from the rat SCI improved locomotion and myelin preservation 8 weeks after rat SCI versus control injections. Because preparation of sufficient quantities of small eMSC for larger studies was not feasible and injection of the large eMSC is problematic, we have developed a procedure to prepare medium-sized eMSC ($\sim 0.35$mm diameter) that can be delivered more reproducibly into the lumbar rat spine. The number of MSC incorporated/capsule in the medium sized capsules was $\sim$5-fold greater than that in small capsules and the total yield of eMSC was ∼ 20-fold higher than that for the small capsules. Assays with all three sizes of eMSC capsules showed that they inhibited TNF-$\alpha$ secretion from activated macrophages in co-cultures, suggesting no major difference in their anti-inflammatory activity in vitro. The in vivo activity of the medium-sized eMSC was tested after injecting them into the lumbar spine 1 day after SCI. Histological analyses 1 week later showed that eMSC reduced levels of activated macrophages measured by IB4 staining and increased white matter sparing in similar regions adjacent to the SCI site. The combined results indicate that ∼ 0.35 mm diameter eMSC reduced macrophage inflammation in regions where white matter was preserved during critical early phases after SCI. These techniques enable preparation of eMSC in sufficient quantities to perform pre-clinical SCI studies with much larger numbers of subjects that will provide functional analyses of several critical parameters in rodent models for CNS inflammatory injury.

Traumatic brain injury (TBI) leads to a cascade of primary and secondary neurodegenerative events, often causing lifelong disabilities. Brain-derived neurotrophic factor (BDNF) is a potential therapeutic for functional recovery of neurons. Unfortunately, BDNF is unstable and expensive, making direct infusion impractical. Therefore, we sought to develop a controlled release formulation to deliver BDNF. Our therapeutic construct encapsulates BDNF in poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), and further encapsulates these NPs in an alginate hydrogel. Encapsulating BDNF within NPs protects and assists in drug delivery, while further encapsulating the BDNF-NPs in alginate enables localization and sustained release. The BDNF-NPs were synthesized and evaluated for size, stability and BDNF release profile. A MATLAB model was developed to determine the approximate quantity of BDNF-NPs needed to evaluate therapeutic efficacy in neurons injured with hydrogen peroxide. We then compared the therapeutic efficacy and BDNF release profile of these BDNF-NPs to our novel alginate/BDNF-NP formulation. We have successfully designed and fabricated a double encapsulation positionally controllable construct that preserves BDNF bioactivity and extends its release. We also demonstrated that very low dosages of BDNF may be equally effective in promoting neuroprotection, thereby potentially reducing therapeutic costs without compromising efficacy. Our novel formulation offers a promising avenue for treating severe TBI and other neurological disorders which would benefit from a long-lasting and positionally controllable neuroprotective treatment. This approach can easily accommodate additional biologics for localized drug delivery with minimal re-formulation.

This research investigates the performance of an assembly micro-atomizer under single-fluid and twin-fluid operational conditions of micro-encapsulation process. Alginate and CaCl₂ aqueous solution are used as the membrane material and hardening agent, respectively. The high speed images were taken to investigate the formation processes of the microcapsules. Results showed that the formation of the microcapsules depends on the instability modes of the liquid column including asymmetry mode, helical mode, sinusoidal mode and spray developing mode as Reynolds number was increased from 221 to 2210. Excitation at resonance frequency of 2.18 kHz of this system resulted in the production of uniform-sized microcapsules. Moreover, SMD equal to 20 μm can be achieved in low GLR under twin-fluid atomization process. It is not easy to achieve by commercial apparatus.

This research investigates the micro-encapsulation process with a pressure-type micro-atomizer. Alginate and CaCl₂ aqueous solution are used as the membrane material and hardening agent, respectively. The high speed images were taken to investigate the formation processes of the microcapsules. Results show that the geometric shape of the microcapsules was sensitive to the droplet flying distant and the concentration of alginate aqueous, however, insensitive to the concentration of CaCl₂ aqueous. Results also show that the membrane thickness of the microcapsules was controlled by the diffusion processes of calcium chloride. An empirical formula was derived to describe the rate change of the membrane thickness in the hardening processes.

Background: Perineural adhesion is a potential complication of manipulating peripheral nerves. Using a model of median nerve manipulation in the carpal tunnel, perineural adhesion preventive effects of an alginate gel formulation were examined.

Methods: After exposing carpal tunnels of Japanese white rabbits and dissecting the median nerve, the gliding floor was excised as much as possible and the transverse carpal ligament was repaired to induce a perineural tissue reaction. Prior to wound closure, 0.5 ml of alginate gel formulation was administered into the right carpal tunnel (formulation group) and 0.5 ml of physiological saline was administered into the left carpal tunnel (control group). At 1, 2, 3, and 6 weeks after treatment, electrophysiological evaluation of thenar distal latency, macroscopic evaluation with adhesion score, and pathological evaluation of carpal tunnel cross sections were performed (N = 4–5 at each time point).

Results: Although distal latency tended to be low in the formulation group, there was no significant difference between the groups according to electrophysiological evaluation. Macroscopic evaluation revealed that the adhesion score was always lower in the formulation group than in the control group; over the course of treatment, it remained unchanged in the formulation group, but peaked at 3 weeks after treatment in the control group. In pathological evaluation, neural perfusion peaked at 2–3 weeks after treatment in both groups; neural perfusion tended to be lower in the formulation group than in the control group.

Conclusions: Results suggested that the peak tissue response associated with nerve dissection occurred 2–3 weeks after treatment and that the repair process started subsequently. The alginate gel formulation modified the surrounding environment of the nerve and promoted repair by acting as a physical barrier against perineural fibrosis. The preventive effect of alginate gel on perineural adhesion may improve treatment outcomes of constrictive neuropathy.

The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in human healthcare. The areas of regenerative medicine and tissue engineering apply the principles of chemistry, biology, and engineering to create new tissues and organs. Here we discuss some of the early work in this field and, in particular, review our studies combining chemistry, materials science, biology, and engineering to create new tissues and organs.

Developments on tissue engineering, especially on tissue regeneration and drug delivery, demand also developments on biomaterials. Research on the preparation methods of biomaterials has exhibited remarkable advances in the recent years. Natural biomaterials, such as chitosan and collagen, or synthetic materials like poly(lactic acid) can be shaped in various forms. The parameters involved in the fabrication processes provide methodologies for control of the materials' properties, such as morphology, biodegradability, mechanical strength, and adhesion. As new applications develop for these materials, the preparation methods have to be optimized to achieve the desired material properties. These properties mostly not only mimic the conditions in the human body, but also may divert the microenvironment of cells in the diseased area in order to promote faster or guided healing and tissue regeneration. This review pays attention on some of the fabrication methods for biomaterial particulates of sizes in the micro- and nanoscale. The views expressed here focus on the many years of experience of the authors with electrostatic and ultrasonic fabrication methods. These methods are still under development and up to now can produce particulates of various sizes down to the nanometer scale with narrow size distributions. Such biomaterials that have extraordinary properties may provide ways for the development of remarkable biomedical applications.

Adult articular cartilage tissue has poor capability of self-repair. Therefore, a variety of tissue engineering approaches are motivated by the clinical need for articular repair. Alginate has been used as a biomaterial for cartilage regeneration. The alginate is a natural polymer that is extracted from seaweeds and purification. However, the main drawback is the immune rejection in vivo. To overcome this problem, we have developed the biocompability of alginate using modified Korbutt method. After alginate was purified, purified alginate microcapsules were used in cartilage regeneration. Chondrocytes were seeded in purified and nonpurified alginate microcapsules, and then cell viability, proliferation and phenotype were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted to confirm mRNA expression on collagen type I and collagen type II for chondrocytes phenotype. Hematoxylin and eosin (H&E) and Safranin-O histological staining showed tissue growth at the interface during the first 10 days. In this study, chondrocytes in purified alginate microcapsules had higher cell viability, proliferation and more phenotype expression than those in nonpurified alginate microcapsules. The results suggest that the purified alginate microcapsule is useful for cartilage regeneration.

In the treatment of wound, a good understanding of the principles of wound healing is essential. A moist wound healing environment is needed. A range of new generation dressings has emerged in addition to traditional dressings such as gauze and tulle gras. These include low-adhesive dressings, transparent dressings, hydrocolloids, hydrogels, alginates, foams, hydrofibres, anti-microbial dressings, de-odouriser dressings and collagen dressings. The choice of dressing depends on a proper assessment of the wound (presence of ischaemia, infection, etc.) and matching the properties of the various dressings available to best meet the individual needs of that particular wound.

Traumatic brain injury (TBI) leads to a cascade of primary and secondary neurodegenerative events, often causing lifelong disabilities. Brain-derived neurotrophic factor (BDNF) is a potential therapeutic for functional recovery of neurons. Unfortunately, BDNF is unstable and expensive, making direct infusion impractical. Therefore, we sought to develop a controlled release formulation to deliver BDNF. Our therapeutic construct encapsulates BDNF in poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), and further encapsulates these NPs in an alginate hydrogel. Encapsulating BDNF within NPs protects and assists in drug delivery, while further encapsulating the BDNF-NPs in alginate enables localization and sustained release. The BDNF-NPs were synthesized and evaluated for size, stability and BDNF release profile. A MATLAB model was developed to determine the approximate quantity of BDNF-NPs needed to evaluate therapeutic efficacy in neurons injured with hydrogen peroxide. We then compared the therapeutic efficacy and BDNF release profile of these BDNF-NPs to our novel alginate/BDNF-NP formulation. We have successfully designed and fabricated a double encapsulation positionally controllable construct that preserves BDNF bioactivity and extends its release. We also demonstrated that very low dosages of BDNF may be equally effective in promoting neuroprotection, thereby potentially reducing therapeutic costs without compromising efficacy. Our novel formulation offers a promising avenue for treating severe TBI and other neurological disorders which would benefit from a long-lasting and positionally controllable neuroprotective treatment. This approach can easily accommodate additional biologics for localized drug delivery with minimal re-formulation.

Microencapsulation of mesenchymal stem cells (MSC) in alginate facilitates cell delivery, localization and survival, and modulates inflammation in vivo. However, we found that delivery of the widely used ∼ 0.5mm diameter encapsulated MSC (eMSC) by intrathecal injection into spinal cord injury (SCI) rats was highly variable. Injections of smaller (∼ 0:2 mm) diameter eMSC into the lumbar spine were much more reproducible and they increased the anti-inflammatory macrophage response around the SCI site. We now report that injection of small eMSC > 2 cm caudal from the rat SCI improved locomotion and myelin preservation 8 weeks after rat SCI versus control injections. Because preparation of sufficient quantities of small eMSC for larger studies was not feasible and injection of the large eMSC is problematic, we have developed a procedure to prepare medium-sized eMSC (∼ 0:35 mm diameter) that can be delivered more reproducibly into the lumbar rat spine. The number of MSC incorporated/capsule in the medium sized capsules was ∼5-fold greater than that in small capsules and the total yield of eMSC was ∼ 20-fold higher than that for the small capsules. Assays with all three sizes of eMSC capsules showed that they inhibited TNF-α secretion from activated macrophages in co-cultures, suggesting no major difference in their anti-inflammatory activity in vitro. The in vivo activity of the medium-sized eMSC was tested after injecting them into the lumbar spine 1 day after SCI. Histological analyses 1 week later showed that eMSC reduced levels of activated macrophages measured by IB4 staining and increased white matter sparing in similar regions adjacent to the SCI site. The combined results indicate that ∼ 0.35 mm diameter eMSC reduced macrophage inflammation in regions where white matter was preserved during critical early phases after SCI. These techniques enable preparation of eMSC in sufficient quantities to perform pre-clinical SCI studies with much larger numbers of subjects that will provide functional analyses of several critical parameters in rodent models for CNS inflammatory injury.