The association between in vivo physicochemical changes and inflammatory responses against alginate based microcapsules

Abstract

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.

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

“…These features are often actively avoided as they are thought to play an important role in graft failure after transplantation. 15,18,52 The islets themselves were also identifiable in the microbeads. Volume rendering of the refraction images enabled observation of the spatial organization of islets (blue) inside the bead structure (green) (Fig.…”

“…Spherical beads are ideal and deviation from this shape can result in a poor healing response and contribute to graft failure. 18,52 XPC imaging also allowed observation of the spatial orientation of islets within the beads and allowed quantification of islet size. Islet volume is an important indicator of islet function and viability.…”

Sequestration of rhBMP-2 into Self-Assembled Polyelectrolyte Complexes Promotes Anatomic Localization of New Bone in a Porcine Model of Spinal Reconstructive Surgery

“…implantation of positively charged polyamino acids has a potential to incite in vivo inflammation depending on chemical formulation, molecular weight, amount implanted, and, therefore, charge density at implantation. 28,29 Therefore, neutralization of the noninteracted PLL was important in this study and this was effectively achieved by heparin as confirmed on zeta potential measurements (Fig. 2).…”

Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials

“…Moreover, studies have reported that the polymer in its primitive form is non-immunogenic relative to PLL and PLO [ 32 ]. Owing to these two crucial traits, and the necessity of incorporating PLL to reduce the pore size of the alginate membrane, Spasojevic et al explored the feasibility of applying a layer of PEG over a membrane already incorporated with PLL-as a PEG-b-PLL diblock copolymer association [ 17 ]. Although other polycations such as chitosan , PLO, and PDL have been attempted to improve the immunoprotective properties of the capsule membrane, they were all found to induce a strong host response in in vivo experiments [ 33 ].…”

“…Although other polycations such as chitosan , PLO, and PDL have been attempted to improve the immunoprotective properties of the capsule membrane, they were all found to induce a strong host response in in vivo experiments [ 33 ]. Reduction in host immune response in terms of less macrophage and fi broblast capsular overgrowth detection was observed in in vivo studies utilizing a PEG-b-PLL grafted copolymer layer on top of the PLL layer in intermediate-G alginate microcapsules [ 17 ].…”