title: Reduction of the inflammatory responses against alginate-poly-L-lysine microcapsules by anti-biofouling surfaces of PEG-b-PLL diblock copolymers.
abstract: Large-scale application of alginate-poly-L-lysine (alginate-PLL) capsules used for microencapsulation of living cells is hampered by varying degrees of success, caused by tissue responses against the capsules in the host. A major cause is proinflammatory PLL which is applied at the surface to provide semipermeable properties and immunoprotection. In this study, we investigated whether application of poly(ethylene glycol)-block-poly(L-lysine hydrochloride) diblock copolymers (PEG-b-PLL) can reduce the responses against PLL on alginate-matrices. The application of PEG-b-PLL was studied in two manners: (i) as a substitute for PLL or (ii) as an anti-biofouling layer on top of a proinflammatory, but immunoprotective, semipermeable alginate-PLL100 membrane. Transmission FTIR was applied to monitor the binding of PEG-b-PLL. When applied as a substitute for PLL, strong host responses in mice were observed. These responses were caused by insufficient binding of the PLL block of the diblock copolymers confirmed by FTIR. When PEG-b-PLL was applied as an anti-biofouling layer on top of PLL100 the responses in mice were severely reduced. Building an effective anti-biofouling layer required 50 hours as confirmed by FTIR, immunocytochemistry and XPS. Our study provides new insight in the binding requirements of polyamino acids necessary to provide an immunoprotective membrane. Furthermore, we present a relatively simple method to mask proinflammatory components on the surface of microcapsules to reduce host responses. Finally, but most importantly, our study illustrates the importance of combining physicochemical and biological methods to understand the complex interactions at the capsules' surface that determine the success or failure of microcapsules applicable for cell-encapsulation.
authors.affiliation: Department of Polymer Chemistry, Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands; Departments of Pathology and Laboratory Medicine, section of Medical Biology, division of immunoendocrinology, University of Groningen, Groningen, The Netherlands.
authors.forename: Milica
authors.initials: M
authors.lastname: Spasojevic
authors.affiliation: Departments of Pathology and Laboratory Medicine, section of Medical Biology, division of immunoendocrinology, University of Groningen, Groningen, The Netherlands.
authors.forename: Genaro A
authors.initials: GA
authors.lastname: Paredes-Juarez
authors.affiliation: Department of Polymer Chemistry, Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands.
authors.forename: Joop
authors.initials: J
authors.lastname: Vorenkamp
authors.affiliation: Departments of Pathology and Laboratory Medicine, section of Medical Biology, division of immunoendocrinology, University of Groningen, Groningen, The Netherlands.
authors.forename: Bart J
authors.initials: BJ
authors.lastname: de Haan
authors.affiliation: Department of Polymer Chemistry, Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands.
authors.forename: Arend Jan
authors.initials: AJ
authors.lastname: Schouten
authors.affiliation: Departments of Pathology and Laboratory Medicine, section of Medical Biology, division of immunoendocrinology, University of Groningen, Groningen, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
mesh_terms: D000327:Adsorption; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D057219:Biofouling; D002214:Capsules / Q000008:administration & dosage; D002460:Cell Line; D020099:Coated Materials, Biocompatible; D004339:Drug Compounding; D006801:Humans; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000464:Alginates; D002214:Capsules; D020099:Coated Materials, Biocompatible; D011108:Polymers; C051546:alginate-polylysine-alginate; D011107:Polylysine; D011092:Polyethylene Glycols