Injectable PEGylated fibrinogen cell-laden microparticles made with a continuous solvent- and oil-free preparation method

Abstract

A new methodology is reported for the continuous, solvent- and oil-free production of photopolymerizable microparticles containing encapsulated human dermal fibroblasts. A precursor solution of cells in photoreactive poly(ethylene glycol) (PEG)-fibrinogen (PF) polymer was transported through a transparent injector exposed to light irradiation before being atomized in a jet-in-air nozzle. Shear rheometry data revealed the crosslinking kinetics of the PF/cell solution, which was then used to determine the amount of irradiation required to partially polymerize the mixture just prior to atomization. The partially polymerized drops of PF/cells fell into a gelation bath for further crosslinking until fully polymerized hydrogel microparticles were formed. As the drops of solution exited the air-in-jet nozzle, their viscosity was designed to be sufficiently high so as to prevent rapid mixing and/or dilution in the gelation bath, but without undergoing complete gelation in the nozzle. Several parameters of this system were varied to control the size and polydispersity of the microparticles, including the cell density, the flow rate and the air pressure in the nozzle. The system was capable of producing cell-laden microparticles with an average diameter of between 88.1 to 347.1μm, and a dispersity of between 1.1 and 2.4, depending on the parameters chosen. Varying the precursor flow rate and/or cell density was beneficial in controlling the size and polydispersity of the microparticles; all microparticles exhibited very high cell viability, which was not affected by these parameters. In conclusion, this dropwise photopolymerization methodology for preparing cell-laden microparticles is an attractive alternative to existing techniques that use harsh solvents/oils and offer limited control over particle size and polydispersity.