Summary: | An immunoencapsulation strategy for pancreatic islets aimed to reduce the risk of rejection in transplanted patients due to the immune response of the host organism is proposed. In this sense, a polyethylene glycol (PEG) hydrogel functionalized with an immunosuppressive antibody (Ab), such as Cytotoxic T-lymphocyte antigen-4 Ig (CTLA4-Ig), would act as both passive and active barrier to the host immune response. To demonstrate the feasibility of this approach, a photopolymerizable-PEG was conjugated to the selected antibody and the PEG-Ab complex was used to coat the islets. Moreover, to preserve the antigen-recognition site of the antibody during the conjugation process, a controlled immobilization method was setup through the attachment of the His-tagged antigen to a solid support. In detail, a gold-coated silicon wafer functionalized with 11-Mercaptoundecanoic acid was used as a substrate for further modification, leading to a nickel(II)-terminated ligand surface. Then, the immobilized antigen was recognized by the corresponding antibody that was conjugated to the PEG. The antibody-PEG complex was detached from the support prior to be photopolymerized around the islets. First, this immobilization method has been demonstrated for the green fluorescent protein (GFP)–anti-green fluorescent protein (Anti-GFP) antigen-antibody pair, as proof of principle. Then, the approach was extended to the immunorelevant B7-1 CTLA-4-Ig antigen-antibody pair, followed by the binding of Acryl-PEG to the immobilized constant region of the antibody. In both cases, after using an elution protocol, only a partial recovery of the antibody-PEG complex was obtained. Nevertheless, the viability and the functional activity of the encapsulated islets, as determined by the glucose-stimulated insulin secretion (GSIS) assay, showed the good compatibility of this approach.
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