(114b) Ultrasound-Derived Acoustic Radiation Force and Cell Therapy: Combined Technologies for Better Bone Repair

Healing of large-scale bone defects remains an unsolved clinical challenge in the orthopaedic realm. Clinical strategies like autografts, allografts, and bone graft substitutes, and preclinical strategies like tissue engineering, and regenerative medicine all have viability as solutions to this challenge and many have been implemented with varying degrees of success. We have sought to combine both clinical and preclinical strategies into a solution for healing large-scale defects by combining cell delivery via a biocompatible, biodegradable hydrogel with low intensity pulsed ultrasound (LIPUS), a clinically proven method of reducing fracture healing time, into one approach that permits the implantation of cell-laden hydrogels into large-scale bone defects followed by intermittent transdermal application of LIPUS-derived acoustic radiation force (ARF) to the implanted cells. Our work has shown elevated levels of mineralization in hydrogels loaded with marrow-derived stem cells and exposed to ARF over the same cells with no ARF. We have also shown the ability to modulate the extent of mineralization by varying the ultrasound intensity and hydrogel composition. In vivo testing has demonstrated healing of critical size defects when ARF was applied to cell-laden hydrogels, something that was not evident without ARF. Finally our in silico modeling allows us to predict the localized forces applied to a cell within the hydrogel for any specific hydrogel stiffness and/or ARF intensity. These preclinical studies bring this novel approach closer to the clinical realm as a novel tool for healing large scale critical size bone defects.