Three dimensionally flocculated proangiogenic microgels for neovascularization

Microparticles encapsulating regenerative medicines have been used in tissue engineering because of their several advantages, including non-invasive drug delivery and controllable drug release rates. However, microparticles implanted in tissue defects are readily displaced by external mechanical forces, decreasing their regenerative efficacy. We hypothesized that a drug-encapsulated colloidal gel formed through colloidal attraction between microparticles would resist displacement at an implant site, and subsequently improve therapeutic efficacy. This hypothesis was examined using a colloidal gel formed from the mixing of negatively charged microgels composed of poly(ethylene glycol) (PEG) and poly(sodium acrylate), and positively charged microgels composed of PEG and poly(vinyl benzyl trimethyl ammonium chloride). The structural strength of the colloidal gel could be tuned with the zeta potential and volumetric ratios of the oppositely charged microgels. Furthermore, the implantation of the colloidal gel, encapsulating vascular endothelial growth factor, significantly increased the vascular density while limiting host inflammation, as compared with the implantation of unary microgel suspensions. This study demonstrates an enhancement in the efficacy of microparticle drug delivery systems by tuning rheological properties of suspensions, which should be useful for the design of a wide array of particulate systems for both tissue engineering and drug delivery.