title: Acoustic droplet-hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness.
abstract: Wound healing is regulated by temporally and spatially restricted patterns of growth factor signaling, but there are few delivery vehicles capable of the "on-demand" release necessary for recapitulating these patterns. Recently we described a perfluorocarbon double emulsion that selectively releases a protein payload upon exposure to ultrasound through a process known as acoustic droplet vaporization (ADV). In this study, we describe a delivery system composed of fibrin hydrogels doped with growth factor-loaded double emulsion for applications in tissue regeneration. Release of immunoreactive basic fibroblast growth factor (bFGF) from the composites increased up to 5-fold following ADV and delayed release was achieved by delaying exposure to ultrasound. Releasates of ultrasound-treated materials significantly increased the proliferation of endothelial cells compared to sham controls, indicating that the released bFGF was bioactive. ADV also triggered changes in the ultrastructure and mechanical properties of the fibrin as bubble formation and consolidation of the fibrin in ultrasound-treated composites were accompanied by up to a 22-fold increase in shear stiffness. ADV did not reduce the viability of cells suspended in composite scaffolds. These results demonstrate that an acoustic droplet-hydrogel composite could have broad utility in promoting wound healing through on-demand control of growth factor release and/or scaffold architecture.
authors.affiliation: Department of Radiology, University of Michigan Health System, Ann Arbor, MI, USA. mfabiill@umich.edu
authors.forename: Mario L
authors.initials: ML
authors.lastname: Fabiilli
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wilson
authors.forename: Frédéric
authors.initials: F
authors.lastname: Padilla
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Martín-Saavedra
authors.forename: J Brian
authors.initials: JB
authors.lastname: Fowlkes
authors.forename: Renny T
authors.initials: RT
authors.lastname: Franceschi
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000528:radiation effects; D004058:Diffusion / Q000528:radiation effects; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry* / Q000528:radiation effects; D055119:Elastic Modulus; D004867:Equipment Design; D019544:Equipment Failure Analysis; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000737:chemistry* / Q000528:radiation effects; D020100:Hydrogels / Q000737:chemistry* / Q000528:radiation effects; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008422:Materials Testing; D013010:Sonication / Q000379:methods*; D013016:Sound; D062211:Spatio-Temporal Analysis; D054457:Tissue Scaffolds
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; D020100:Hydrogels; D036341:Intercellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2
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