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Islets encapsulated in immunoprotective microcapsules are being proposed as an alternative for insulin therapy for treatment of type 1 diabetes. Many materials for producing microcapsules have been proposed but only alginate does currently qualify as ready for clinical application. However, many different alginate-based capsule systems do exist. A pitfall in the field is that these systems are applied without a targeted strategy with varying degrees of success as a consequence. In the current review, the different properties of alginate-based systems are reviewed in view of future application in humans. The use of allogeneic and xenogeneic islet sources are discussed with acknowledging the different degrees of immune protection the encapsulation system should supply. Also issues such as oxygen supply and the role of danger associated molecular patterns (DAMPS) in immune activation are being reviewed. A common property of the encapsulation systems is that alginates for medical application should have an extreme high degree of purity and lack pathogen-associated molecular patterns (PAMPs) to avoid activation of the recipient’s immune system. Up to now, non-inflammatory alginates are only produced on a lab-scale and are not yet commercially available. This is a major pitfall on the route to human application. Also the lack of predictive pre-clinical models is a burden. The principle differences between relevant innate and adaptive immune responses in humans and other species are reviewed. Especially, the extreme differences between the immune system of non-human primates and humans are cumbersome as non-human primates may not be predictive of the immune responses in humans, as opposed to the popular belief of regulatory agencies. Current insight is that although the technology is versatile major research efforts are required for identifying the mechanical, immunological, and physico-chemical requirements that alginate-based capsules should meet for successful human application.

Citation for published version (APA): de Vos, P., Spasojevic, M., de Haan, B., & Faas, M. M. (2012). The association between in vivo physicochemical changes and inflammatory responses against alginate based microcapsules. Biomaterials, 33(22), 5552-5559. a b s t r a c t Application of alginate-polylysine (PLL) capsules for immunoisolation of living cells are suffering from a varying degree of success and large lab-to-lab variations. In this study we show that these differences in success rates can be attributed to alginate dependent essential physicochemical changes of the properties of capsules in vivo that will render the capsules more susceptible to inflammatory responses. Capsule properties were studied before and after implantation by XPS, by immunocytochemistry, and by measuring zeta potentials. We studied a capsule type which provokes for unknown reasons a strong inflammatory response, i.e. high-guluronic (G) alginate capsules and a capsule type with near identical physicochemical properties but which evokes a minimal inflammatory response, i.e. intermediate-G alginate capsules. The cause of the difference in response was a decrease in nitrogen content on high-G capsules due to detachment of PLL in vivo and an increase of the zeta-potential. Our data illustrate an important overlooked phenomena; the physicochemical properties are not necessarily the properties after exposure to the in vivo microenvironment and might induce undesired inflammatory responses and failure of encapsulated cellular grafts.

No abstract

Nanostructured nickel-iron-tungsten alloy coatings were electrodeposited from an ammonia citrate bath on steel and copper substrates at current densities in the range of 50 to 300 mA cm −2 . The contents of iron and tungsten in the alloy increase and that of nickel decreases with increasing deposition current density. At current densities below 100 mA cm −2 , smooth shiny coatings with no cracks and craters are deposited. Higher current densities result in matte coatings developing cracks and craters. XRD analysis showed that the coatings contain nanocrystals of FCC structured solid solution of iron and tungsten in nickel embedded in an amorphous matrix. Increasing deposition current density leads to an increase in the amorphous phase content and a decrease in both the content and mean crystallite size of the FCC phase. The coatings with an increased amorphous phase content and a decreased mean FCC crystallite size exhibit lower magnetization and reduced hardness. During annealing at temperatures up to 400 • C, the alloy undergoes structural relaxation along with short-range structural arrangement, resulting in increased magnetization and hardness. At temperatures above 500 • C, annealing leads to amorphous phase crystallization and crystal grain growth in the FCC solid solution, thus leading to reduction in both magnetization and hardness.