Ultrasound-Driven ex-vivo Engineering of Tissue-Guiding Hydrogels for Bone Regeneration

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This project aims at the development of ultrasound-based methodology to create mechanically, structurally and biologically tunable tissue-guiding ex-vivo constructs for regeneration of bone defects. Ultrasound will be supplied in different modes throughout the project development. Via application of ultrasound standing waves, patterned organization of Mesenchymal Stromal Cells (MSCs) and liposome-encapsulated Bone Morphogenetic Protein-2 (BMP-2) growth factor will be achieved in the in-situ polymerizing gel. This will accomplish extracellular matrix organization mirroring cellular alignment in the scaffolds, contributing to the development of anisotropic tissue constructs. Spatially and temporally controlled on-demand release of BMP-2 from the immobilized liposomes will be supplied by a high-intensity acoustic burst. Thereby, the required growth-factor concentration can be considerably reduced, which is highly appealing in the clinical setting due to the BMP-2-associated side effects. Additionally, Low-Intensity Pulsed Ultrasound will be applied to promote cellular survival in the entire construct and to further reduce the BMP-2 concentration necessary for efficient osteogenic differentiation of the cells. The resultant scaffolds will be mechanically tested and their tissue guiding properties will be assessed. Scanning acoustic biomicroscopy (SAM) will be used for longitudinal imaging of the maturing scaffolds, yielding additional information on the evolution of mechanical material properties. The methodology proposed here can be further adapted by varying cell type, biofactor and polymerizing gel for ex-vivo design of constructs aimed at regeneration of other tissues.