Encapsulation of pancreatic beta cells

Immunoisolation of pancreatic beta cells is a promising approach for the treatment of type I diabetes. In this thesis, a vibrating nozzle technology was utilised to reproducibly generate 1% alginate microparticles with an average diameter of 200 μm±19 S.D. This technology further enabled the application of fluidised bed bioreactor owing to high uniformity of particles, an important parameter for achieving homogeneous fluidisation. Experimental data collected from the cultivation of cells in fluidised culture was shown to provide a promising solution for handling encapsulated cells from manufacturing phase to clinical sites, which is currently a challenging issue for cell-based therapies. A reduction in beta cells insulin-secreting ability was observed after two weeks of static culture. This problem was addressed by investigating a 3- dimentional culturing technique and a novel polyelectrolyte multilayer (PEM) coating approach. Concave agarose micro-wells were used to culture robust pancreatic beta cell spheroids that enhanced cell-cell contact. Additionally, the novel PEM coating using Ca2+ pre- conditioning improved cell function while providing immunoisolation from cytokines, and reducing the total volume of the graft. This work presented an effective immunoisolation and culturing system to improve cells survival rate, which hopes to bring a closer step towards therapeutic transplantation

Calcium pre-conditioning substitution enhances viability and glucose sensitivity of pancreatic beta-cells encapsulated using polyelectrolyte multilayer coating method

Type I diabetics are dependent on daily insulin injections. A therapy capable of immunoisolating pancreatic beta-cells and providing normoglycaemia is an alternative since it would avoid the late complications associated with insulin use. Here, 3D-concave agarose micro-wells were used to culture robust pancreatic MIN-6 cell spheroids within 24 hours that were shown to exhibit cell-cell contact and uniform size (201 ± 2 μm). A polyelectrolyte multilayer (PEM) approach using alginate and poly-l-lysine was employed to coat cell spheroids. In comparison to conventional PEM, use of a novel Ca(2+) pre-coating step enhanced beta-cells viability (89 ± 6%) and metabolic activity since it reduced the toxic effect of the cationic polymer. Pre-coating was achieved by treating MIN-6 spheroids with calcium chloride, which enabled the adhesion of anionic polymer to the cells surface. Pre-coated cells coated with four bilayers of polymers were successfully immunoisolated from FITC-mouse antibody and pro-inflammatory cytokines. Novel PEM coated cells were shown to secret significantly (P < 0.05) different amounts of insulin in response to changes in glucose concentration (2 vs. 20 mM). This work presents a 3D culture model and novel PEM coating procedure that enhances viability, maintains functionality and immunoisolates beta-cells, which is a promising step towards an alternative therapy to insulin

Physical structuring of injectable polymeric systems to controllably deliver nanosized extracellular vesicles

Extracellular vesicles (EVs) are emerging as a promising alternative approach to cell‐therapies. However, to realize the potential of these nanoparticles as new regenerative tools, healthcare materials that address the current limitations of systemic administration need to be developed. Here, two technologies for controlling the structure of alginate based microgel suspensions are used to develop sustained local release of EVs, in vitro. Microparticles formed using a shearing technique are compared to those manufactured using vibrational technology, resulting in either anisotropic sheet‐like or spheroid particles, respectively. EVs harvested from preosteoblasts are isolated using differential ultracentrifugation and successfully loaded into the two systems, while maintaining their structures. Promisingly, in addition to exhibiting even EV distribution and high stability, controlled release of vesicles from both structures is exhibited, in vitro, over the 12 days studied. Interestingly, a significantly greater number of EVs are released from the suspensions formed by shearing (69.9 ± 10.5%), compared to the spheroids (35.1 ± 7.6%). Ultimately, alterations to the hydrogel physical structures have shown to tailor nanoparticle release while simultaneously providing ideal material characteristics for clinical injection. Thus, the sustained release mechanisms achieved through manipulating the formation of such biomaterials provide a key to unlocking the therapeutic potential held within EVs

Physical structuring of injectable polymeric systems to controllably deliver nanosized extracellular vesicles

Extracellular vesicles (EVs) are emerging as a promising alternative approach to cell‐therapies. However, to realize the potential of these nanoparticles as new regenerative tools, healthcare materials that address the current limitations of systemic administration need to be developed. Here, two technologies for controlling the structure of alginate based microgel suspensions are used to develop sustained local release of EVs, in vitro. Microparticles formed using a shearing technique are compared to those manufactured using vibrational technology, resulting in either anisotropic sheet‐like or spheroid particles, respectively. EVs harvested from preosteoblasts are isolated using differential ultracentrifugation and successfully loaded into the two systems, while maintaining their structures. Promisingly, in addition to exhibiting even EV distribution and high stability, controlled release of vesicles from both structures is exhibited, in vitro, over the 12 days studied. Interestingly, a significantly greater number of EVs are released from the suspensions formed by shearing (69.9 ± 10.5%), compared to the spheroids (35.1 ± 7.6%). Ultimately, alterations to the hydrogel physical structures have shown to tailor nanoparticle release while simultaneously providing ideal material characteristics for clinical injection. Thus, the sustained release mechanisms achieved through manipulating the formation of such biomaterials provide a key to unlocking the therapeutic potential held within EVs

Sitúate : revista digital de situaciones de aprendizaje

Esta tarea está basada en el diseño y realización de actividades relacionadas con el mundo de las palabras, de su correcta dicción y escritura, con gran tratamiento TIC en alguna de sus partes. Durante el primer trimestre escolar un tanto por ciento elevado alumnado han preguntado sobre determinadas letras en palabras con intención de escribirlas mejor ( b ó v, mudita o sin ella…). Sorprende y maravilla aún más como también demandan información sobre la tilde. Se potencia a aquellos que demandan más, e indudablemente se ayuda y fortalece también a aquellos que no lo demandan o “no lo han hecho todavía”.ES

Factors influencing safety and efficacy of intravenous iron-carbohydrate nanomedicines: From production to clinical practice

Iron deficiency is an important subclinical disease affecting over one billion people worldwide. A growing body of clinical records supports the use of intravenous iron-carbohydrate complexes for patients where iron replenishment is necessary and oral iron supplements are either ineffective or cannot be tolerated by the gastrointestinal tract. A critical characteristic of iron-carbohydrate drugs is the complexity of their core-shell structure, which has led to differences in the efficacy and safety of various iron formulations. This review describes parameters influencing the safety and effectiveness of iron-carbohydrate complexes during production, storage, handling, and clinical application. We summarized the physicochemical and biological assessments of commercially available iron carbohydrate nanomedicines to provide an overview of publicly available data. Further, we reviewed studies that described how subtle differences in the manufacturing process of iron-carbohydrate complexes can impact on the physicochemical, biological, and clinical outcomes of original product versus their intended copies or so-called iron "similar" products