The Quest for Anti-inflammatory and Anti-infective Biomaterials in Clinical Translation.

Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date, however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients, such as infection and inflammation. Different strategies are needed to address the regeneration of organs that have been damaged by infection or inflammation for successful clinical translation. Therefore, the real quest is for multifunctional biomaterials with combined properties that can combat infections, modulate inflammation, and promote regeneration at the same time. These strategies will necessitate the inclusion of methodologies for management of the cellular and signaling components elicited within the local microenvironment. In the development of such biomaterials, strategies range from the inclusion of materials that have intrinsic anti-inflammatory properties, such as the synthetic lipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC), to silver nanoparticles that have antibacterial properties, to inclusion of nano- and micro-particles in biomaterials composites that deliver active drugs. In this present review, we present examples of both kinds of materials in each group along with their pros and cons. Thus, as a promising next generation strategy to aid or replace tissue/organ transplantation, an integrated smart programmable platform is needed for regenerative medicine applications to create and/or restore normal function at the cell and tissue levels. Therefore, now it is of utmost importance to develop integrative biomaterials based on multifunctional biopolymers and nanosystem for their practical and successful clinical translation

Dise?o, procura y construcci?n del condominio residencial Los Defensores

El proyecto Dise?o, Procura y Construcci?n del condominio residencial los Defensores es una obra privada que busca innovar con la propuesta de contar con ?reas de esparcimiento y residencial, por ser de car?cter masivo se encuentra en el mercado de proyectos econ?micos, sin embargo ofrece mejor distribuci?n y mayores ?reas que los departamentos convencionales, esto representa una gran oportunidad de negocio para la empresa inmobiliaria la constructora S.A. El proyecto se encuentra ubicado en el distrito de Chorrillos-Per? y est? formado por 3 bloques de 10 pisos, y 4 departamentos por piso, en total 120 departamentos. En este sentido la meta para el desarrollo de tesis es implantar un modelo de gesti?n de proyectos para el sector construcci?n, se planten los siguientes objetivos. Dentro de su estructura organizativa se encuentra la Constructora encargada de la ejecuci?n de proyectos, quienes entregan el proyecto terminado al ?rea de ventas de la Inmobiliaria para su posterior puesta en venta. Para esto la empresa hace uso de herramientas de gesti?n para la planificaci?n y ejecuci?n de este tipo de proyectos como algunos est?ndares indicados en el PMI. Adem?s, como parte de un an?lisis de optimizaci?n se analizan dos escenarios respecto de los sistemas constructivos tradicionales. El proyecto cuenta con un equipo de Gesti?n de Proyectos encabezado por el Project Manager quien a su vez cuenta con un equipo multidisciplinario para cada una de las fases del proyecto

Mental Imagery and Visual Working Memory

Visual working memory provides an essential link between past and future events. Despite recent efforts, capacity limits, their genesis and the underlying neural structures of visual working memory remain unclear. Here we show that performance in visual working memory - but not iconic visual memory - can be predicted by the strength of mental imagery as assessed with binocular rivalry in a given individual. In addition, for individuals with strong imagery, modulating the background luminance diminished performance on visual working memory and imagery tasks, but not working memory for number strings. This suggests that luminance signals were disrupting sensory-based imagery mechanisms and not a general working memory system. Individuals with poor imagery still performed above chance in the visual working memory task, but their performance was not affected by the background luminance, suggesting a dichotomy in strategies for visual working memory: individuals with strong mental imagery rely on sensory-based imagery to support mnemonic performance, while those with poor imagery rely on different strategies. These findings could help reconcile current controversy regarding the mechanism and location of visual mnemonic storage

Alternativ splicing i mänsklig sjukdom

Exoner är de sekvenser i DNA vilka rymmer koden för proteiner i människan och i alla andra organismer. Intronerna, vilka utgör utrymmet mellan exoner, består av ickekodande sekvenser och kontrollelement. Exoner tillhörande en gen måste inte alltid inkluderas i den slutliga mRNA produkten, alternativ splicing tillåter exkludering av vissa sekvenser och gör att en gen kan ha mer än en mRNA produkt, därigenom kan en gen koda för flera olika proteiner. Alternativ splicing är ett fält som snabbt utvecklas och dess relevans för många sjukdomar har blivit uppenbar. Detta arbete går igenom ett flertal av dessa sjukdomar för att sammanställa ny forskning och tydliggöra rollen av alternativ splicing i dem. De sjukdomar som undersökts är cystisk fibros, ärftlig frontotemporal dementia, systemisk lupus erythematosus, aniridi, myotonisk dystrofi, amyotrophic lateral sclerosoch familial dysautonomia. Dessa sjukdomar har involvering av alternativ splicing, de genetiska processerna bakom dem är dock mycket olika och kan visa på de många sätt alternativ splicing kan påverka cell och kroppsfunktion. Målet med arbetet är en översiktlig bild av framstegen som gjorts och vilken forskning som nu bedrivs

Controlled delivery of human cells by temperature responsive microcapsules

Cell therapy is one of the most promising areas within regenerative medicine. However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into. Encapsulation of individual cells has been proposed as a means of increasing cell viability. In this study, we developed a facile, high throughput method for creating temperature responsive microcapsules comprising agarose, gelatin and fibrinogen for delivery and subsequent controlled release of cells. We verified the hypothesis that composite capsules combining agarose and gelatin, which possess different phase transition temperatures from solid to liquid, facilitated the destabilization of the capsules for cell release. Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line—human umbilical vein endothelial cells (HUVECs). While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation

Correction: W.C. Mak, et al. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules. J. Funct. Biomater. 2015, 6, 439-453

Recently, we found a mistake in Figure 4D in our previously published paper[...

The quest for anti-inflammatory and anti-infective biomaterials in clinical translation

Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients such as infection and inflammation. Different strategies are needed to address the regeneration of organs that have been damaged by infection or inflammation for successful clinical translation. Therefore, the real quest is for multi-functional biomaterials with combined properties that can combat infections, modulate inflammation and promote regeneration at the same time. These strategies will necessitate the inclusion of methodologies for management of the cellular and signaling components elicited within the local microenvironment. In the development of such biomaterials, strategies range from the inclusion of materials that have intrinsic anti-inflammatory properties, such as the synthetic lipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC), to silver nanoparticles that have anti-bacterial properties, to inclusion of nano- and micro-particles in biomaterials composites that deliver active drugs. In this present review, we present examples of both kinds of materials in each group along with their pros and cons. Thus, as a promising next generation strategy to aid or replace tissue/organ transplantation, an integrated smart programmable platform is needed for regenerative medicine applications to create and/or restore normal function at the cell and tissue levels. Therefore, now it is an utmost important to develop integrative biomaterials based on multi-functional biopolymers and nanosystem for their practical and successful clinical translation

Functional fabrication of recombinant human collagen–phosphorylcholine hydrogels for regenerative medicine applications

The implant-host interface is a critical element in guiding tissue or organ regeneration. We previously developed hydrogels comprising interpenetrating networks of recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) as substitutes of the corneal extracellular matrix that promote endogenous regeneration of corneal tissue. To render them functional for clinical application, we have now optimized their composition and thereby enhanced their mechanical properties. We have demonstrated that such optimized RHCIII-MPC hydrogels are suitable for precision femtosecond laser cutting to produce complementing implants and host surgical beds for subsequent tissue welding. This avoids the tissue damage and inflammation associated with manual surgical techniques, thereby leading to more efficient healing. Although we previously demonstrated in clinical testing that RHCIII-based implants stimulated cornea regeneration in patients, the rate of epithelial cell coverage of the implants needs improvement, e.g. modification of the implant surface. We now show that our 500 μm thick RHCIII-MPC constructs comprising over 85% water, are suitable for microcontact printing with fibronectin. The resulting fibronectin micropatterns promote cell adhesion, as compared to the bare RHCIII-MPC hydrogel. Interestingly, a pattern of 30 μm wide fibronectin stripes enhanced cell attachment and showed highest mitotic rates, an effect that potentially can be utilized for faster integration of the implant. We have therefore shown that laboratory-produced mimics of naturally occurring collagen and phospholipids can be fabricated into robust hydrogels that can be laser profiled and patterned to enhance their potential function as artificial substitutes of donor human corneas.We thank Dr. Chyan-Jang Lee for establishing the GFP-HCEC cell line used for this study, and Ms. Kimberley Merrett for assistance in characterization of the hydrogels. We also thank Dr. Sadhana Kulkani and David Priest, University of Ottawa Eye Institue, for assistance with the laser cutting study; and Dr. Joanne M. Hackett (currently at Cambridge University Health Partners) for assistance with preliminary cell culture/biocompatibility studies during optimization of the RHCIII-MPC hydrogels. We thank Johannes Junger and Michael Baumann, MLase AG, for help with the UV crosslinking, and the Medical Devices Bureau, Health Canada, for use of the SEM system. We gratefully acknowledge funding from an NSERC-CIHR Canada Collaborative Health Research Project grant (M.G.) and subsequent funding for an EU Nanomedicine ERAnet project "I-CARE" to M.G., R.V. and MLase AG, through the Swedish Research Council, Research Council of Lithuania and VDI Germany, respectively.</p