The aim of this work was to assess the diffusive properties of poly(ethylene glycol) diacrylate (PEGDA)‐based hydrogels, derived from low MW prepolymers, in view of potential biomedical applications. Several hydrogels were synthesized through UV irradiation of PEGDA solutions for different exposure times. Swelling measurements in distilled water were performed to estimate the yielded crosslink density, while swelling tests at 37 °C in selected media allowed to analyze the mesh size changes induced by various pH and ionic strength (IonS) conditions. The transport of glucose and insulin through thin hydrogel membranes was finally assessed in a modified Ussing chamber at physiological values of pH and IonS (7.4 and 150 mM, respectively). Results showed that the swelling was dependent on the IonS (with swelling reductions up to 20–30% for IonS increases in the range 0–300 mM) and, to a lesser extent, on the pH of the surrounding medium (with swelling increments of about 10% for increasing pH in the range 2.5–11). All hydrogels were also permeable to glucose and insulin, which displayed comparable diffusion coefficients (in the order of 10−6 cm2/s). Specific interactions between glucose and the polymer chains were evidenced by values of the partition coefficient higher than unity. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44380.
In the present work, we investigated the potential of novel semi-interpenetrating polymer network (semi-IPN) cryogels, obtained through ultraviolet exposure of aqueous mixtures of poly(ethylene glycol) diacrylate and type I collagen, as tunable offthe-shelf platforms for 3D cancer cell research. We synthesized semi-IPN cryogels with variable collagen amounts (0.1% and 1% w/v) and assessed the effect of collagen on key cryogel properties for cell culture, for example, porosity, degradation rate and mechanical stiffness. Then, we investigated the ability of the cryogels to sustain the long-term growth of two pancreatic ductal adenocarcinoma (PDAC) cell populations, the parenchymal Panc1 cells and their derived cancer stem cells. Results revealed that both cell lines efficiently infiltrated, attached and expanded in the cryogels over a period of 14 days. However, only when grown in the cryogels with the highest collagen concentration, both cell lines reproduced their characteristic growth pattern previously observed in collagen-enriched organotypic cultures, biomimetic of the highly fibrotic PDAC stroma. Cellular preembedding in Matrigel, that is, the classical approach to develop/grow organoids, interfered with an efficient intrascaffold migration and growth. Although preliminary, these findings highlight the potential of the proposed cryogels as reproducible and tunable cancer cell research platforms.
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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