title: Electrostatically self-assembled biodegradable microparticles from pseudoproteins and polysaccharide: fabrication, characterization, and biological properties.
abstract: Electrostatically self-assembling hybrid microparticles derived from novel cationic unsaturated arginine-based poly(ester amide) polymers (UArg-PEA) and anionic hyaluronic acid (HA) were fabricated into sub-micron-sized particles in aqueous medium with subsequent UV crosslinking treatment to stabilize the structure. These hybrid microparticles were characterized for size, charge, viscosity, chemical structure, morphology, and biological properties. Depending on the feed ratio of cationic UArg-PEA to anionic HA, the crosslinked microparticles formed spherical structures of 0.772-22.08 μm in diameter, whereas the uncrosslinked microparticles formed a core with an outer petal-like structure of 2.49-15 μm in diameter. It was discovered that the morphological structure of the self-assembled microparticles had a profound influence on their biological properties. At a 1:1 feed ratio of UArg-PEA to HA, the uncrosslinked microparticles showed no cytotoxicity toward NIH 3T3 fibroblasts at concentrations up to 20 μg/mL, and the crosslinked particles exhibited no cytotoxicity at concentrations up to 10 μg/mL. The UArg-PEA/HA hybrid microparticles exhibited a significantly lower macrophage-induced proinflammatory response (via TNF-α) than that from a pure hyaluronic acid control while retaining the beneficial anti-inflammatory IL-10 production by HA. The UArg-PEA/HA microparticles also stimulated size-dependent induction of arginase activity. Therefore, self-assembling these two types of biomaterials in a favorable nontoxic aqueous environment, having complementary biological properties like those of the currently reported UArg-PEA/HA hybrid microparticles, may provide a new class of biomaterials to improve the overall tissue microenvironment for promoting wound healing.
authors.affiliation: Department of Chemistry and Chemical Biology, ‡Department of Biological and Environmental Engineering, ∥Department of Fiber Science and Apparel Design, ⊥Department of Biomedical Engineering, Cornell University , Ithaca, New York 14853-4401, United States.
authors.forename: Alicia N
authors.initials: AN
authors.lastname: Potuck
authors.forename: Beth L
authors.initials: BL
authors.lastname: Weed
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Leifer
authors.forename: C C
authors.initials: CC
authors.lastname: Chu
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D013499:Surface Properties; D014783:Viscosity
chemical_list: D001672:Biocompatible Materials; D011134:Polysaccharides; D006820:Hyaluronic Acid