Semi-interpenetrating network hyaluronic acid microgel delivery systems in micro-flow

Semi-interpenetrating hyaluronic acid (HA)-based hydrogel microparticles in a form of spherical or biconcave shape have been developed, suitable for injectable therapies with high safety profile in micro-flow. [Display omitted] Macroscopic hydrogels are commonly used as injectable scaffolds or fillers, however they may easily obstruct blood vessels, which poses risks and limits their clinical use. In the present study, three types of hyaluronic acid (HA)-based hydrogel micro-particles with non-covalent, covalent semi-interpenetrating and conventional 3D molecular networks, have been designed, fabricated and characterized. The micro-particles are spherical, biconcave or irregular in shape and their diameter ranged between 2.5 and 3.5 µm; their suspensions exhibit a tuneable viscosity, shear-thinning behaviour, dynamic stability and dispersity in microfluidic flow as a result of their specific particulate nature, providing thus a well-controlled injectable platform. Hydrogel particle suspensions also demonstrate an enhanced safety profile, in terms of the dispersity, cell safety, and hemocompatibility. In addition, Rhodamine 6G has successfully been loaded and released from the particles as a model for drug delivery. Functionalisation of hydrogel microparticles using synthetic polymers has been proven to be a cost-effective way to achieve desirable rheological properties and flow dynamic stability with improved physicochemical properties and biocompatibility in vitro, showing promise as a multifunctional biomedical material for various advanced surgical devices and therapies.