Nanofilm generated non-pharmacological anabolic bone stimulus.

Abstract

Stimulus-responsive nanomaterials have mainly been employed to ablate or destroy tissues or to facilitate controlled release of drugs or biologics. Herein, we demonstrate the potential of stimulus-responsive nanomaterials to promote tissue regeneration via a non-pharmacological and noninvasive strategy. Thin nanofilms of an optically-absorbing organic dye or nanoparticle (single-walled graphene nanoribbons [SWOGNR]) were placed over (without touching the skin) a rodent femoral fracture site. A nanosecond pulsed near-infrared laser diode was employed to generate photoacoustic (PA) signals from the nanofilms. X-ray micro-computed tomography (microCT), histology, and mechanical testing results showed that daily PA stimulations of upto 45 min for 6 weeks (complete fracture healing) do not adversely affect bone regeneration and quality. Further, microCT and histological analysis showed 10 min daily stimulation for 2 weeks significantly increases bone quantity at the fracture sites of rats exposed to the nanoparticle-generated PA signals. In these rats, up to threefold increase in bone volume to callus volume ratio and twofold increase in bone mineral density within the callus were noted, compared to rats that were not exposed to the photoacoustic signals. The results taken together indicate that nanofilm-generated photoacoustic signals serve as an anabolic stimulus for bone regeneration. The results, in conjugation with the ability of these nanofilms to serve as PA contrast agents, present opportunities toward the development of integrated noninvasive imaging and noninvasive or invasive treatment strategies for bone loss due to disease or trauma.