Controlled drug delivery in tissue regeneration

Hydrogels are frequently used to deliver exogenous biomolecules like growth factors in tissue regeneration. With conventional hydrogels, there is a limited ability to spatially and temporally control drug release, especially after a hydrogel is implanted. This critical limitation has ultimately hindered the translation of growth factor-based therapies in tissue regeneration. 

We are exploring two ultrasound-based approaches for controlling release of biomolecules. First, we have designed composite hydrogels containing phase-shift emulsions. Biomolecular payloads, which are initially contained in the phase-shift emulsion, are released by focused ultrasound in a process termed acoustic droplet vaporization. Second, in collaboration with the Franceschi lab, we are using ultrasound to thermally activate cells  containing heat-activated gene switches. We are using these approaches to stimulate the growth of blood vessels and bone.. 

Collaborators: Andrew Putnam, Renny Franceschi, Oliver KripfgansJan Stegemann, Xueding Wang

Modulation of biophysical properties of hydrogels

In addition to biochemical cues, cellular behaviors are influenced by biophysical cues in their local microenvironment. Conventional hydrogels possess static biophysical properties like stiffness and matrix porosity. Therefore, the ability to dynamically change biophysical properties of a hydrogel is limited. 

We are using focused ultrasound to modulate cellular behaviors by dynamically altering biophysical properties of composite hydrogels.  Using acoustic droplet vaporization, we can generate two distinct morphological features - localized hydrogel compaction and micropore formation. We are using these approaches to induce cell differentiation as well as enhance cell migration and blood vessel formation. 

Collaborators: Brendon Baker, Renny Franceschi, Jon Estrada, Mitra Aliabouzar