Sequential payload release from acoustically-responsive scaffolds using focused ultrasound

摘要

Regenerative processes, such as angiogenesis and osteogenesis, often require multiple growth factors (GFs) with distinct spatiotemporal patterns and expression sequences. Within tissue engineering, hydrogel scaffolds are commonly used for exogenous GF delivery. However, direct incorporation of GFs within conventional hydrogels does not afford spatiotemporally controlled delivery since release is governed by passive mechanisms that cannot be actively controlled after the scaffold is implanted. We have developed acoustically-responsive scaffolds (ARSs), which are fibrin scaffolds doped with payload-containing, sonosensitive emulsions. Payload release from ARSs can be controlled non-invasively and on-demand using focused, megahertz-range ultrasound. In this in vitro study, we develop and characterize ARSs that enable sequential release of two surrogate, fluorescent payloads using consecutive ultrasound exposures at different acoustic pressures. ARSs were generated with various combinations and volume fractions of perfluoropentane (PFP), perfluorohexane (PFH), and perfluoroheptane (PFHep) emulsions. Acoustic droplet vaporization and inertial cavitation thresholds correlated with the boiling point/molecular weight of the perfluorocarbon while payload release correlated inversely. Payload release was longitudinally measured and followed a sigmoidal trend versus acoustic pressure. PFP and PFH emulsions were stabilized when incorporated into ARSs with PFHep emulsion. These results highlight the potential of using ARSs for sequential, dual payload release for tissue regeneration.