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.

<p>Applications of Graphene and Its Derivatives in Bone Repair: Advantages for Promoting Bone Formation and Providing Real-Time Detection, Challenges and Future Prospects</p>

“…In addition, it has been indicated that GDs could be applied to real-time detection of bone repair process. After GDs were modified with functional groups or combined with fluorescent/magnetic molecules, the imaging efficiency of the GDs-containing composites with various detection equipment such as computed tomography (CT), 48 ultrasound 49 and nuclear magnetic resonance (NMR) 50 could be significantly improved, by which the structural integrity, 51 tumorigenicity, 52 degradability 53 and mineralization 54 of the composites could be real-timely evaluated, which was definitely helpful for further and deeper study of the bone repair process. Compared with most of other substrate contrast agents, GDs could be more conducive to the quantitative control of loaded fluorescent markers or paramagnetic substances 55 based on their excellent conductivity and large SSA.…”

Development of Graphene‐Based Materials in Bone Tissue Engineaering

“…[ 238 , 239 , 240 ] In addition, the low‐power NIR facilitates wound healing, bone repair, angiogenesis, etc. [ 241 , 242 , 243 ] In this process, the PTAs with high photothermal conversion efficiency exert the largest agglomerative thermal effect, to achieve a fixed‐point temperature rise and then heat the tumor, while the normal tissue is not damaged by heat. Therefore, the photothermal conversion efficiency of PTAs is very important.…”

NIR light-assisted phototherapies for bone-related diseases and bone tissue regeneration: A systematic review

“…The photocurrent upon two photon excitation of this small sized C 3 N 4 sheet would induce a charge transfer and increased cytosolic Ca 2+ accumulation, resulting in enhanced osteogenic differentiation of stem cells and new bone formation. In addition, single‑walled graphene nanoribbons have been reported to generate photoacoustic signals under 905 nm NIR laser radiation, which could serve as an anabolic stimulus for noninvasive bone defect repair in a rodent femoral fracture site 103 .…”