Elastin-like Recombinamers\nas a Biotechnological Platform\nfor the Development of Cytokine-Functionalized Materials

Oncostatin M (OSM)\nand leukemia inhibitory factor (LIF)\nare pleiotropic\ncytokines from the interkeukine-6 family, associated with several\ndisorders, and present significant potential in biomedicine. However,\ntheir therapeutic use is highly constrained by factors such as short\ncirculating half-life and narrow therapeutic window. The conjugation\nof cytokines with elastin-like recombinamers (ELR) holds the potential\nto circumvent these limitations due to the ability of self-assembling\nupon a thermal stimulus, remarkable biocompatibility, and ease of\nprocessing. In this work, we report on the development of genetically\nengineered hybrid ELR conjugates by fusing the DNA sequences coding\nfor murine/human OSM and LIF into the C-terminus of an ELR. The resulting\nhybrid fusion proteins demonstrated to retain the thermal properties\nof the ELR, which enabled the nonchromatographic purification by employing\nsimple hot/cold cycles. Nanoparticles and free-standing films were\nobtained by self-assembly and solvent casting, respectively, using\nenvironmentally friendly processes (mild conditions and water-based\nmethods). Both materials were characterized for their properties,\nrevealing the absence of hemotoxicity upon contact with red blood\ncells and promising features for potential therapeutic applications.\nOverall, this work represents a step forward in the development of\nadvanced functionalized biomaterials suitable for localized cytokine\ntherapy.