No abstract

Diabetic foot ulcers (DFUs), the most serious complication of diabetes mellitus, can induce high morbidity, the need to amputate lower extremities, and even death. Although many adjunctive strategies have been applied for the treatment of DFUs, the low treatment efficiency, potential side effects, and high cost are still huge challenges. Recently, nanomaterial-based drug delivery systems (NDDSs) have achieved targeted drug delivery and controlled drug release, offering great promises in various therapeutics for diverse disorders. Additionally, the radial extracorporeal shock wave (rESW) has been shown to function as a robust trigger source for the NDDS to release its contents, as the rESW harbors a potent capability in generating pressure waves and in creating the cavitation effect. Here, we explored the performance of oxygen-loaded nanoperfluorocarbon (Nano-PFC) combined with the rESW as a treatment for DFUs. Prior to in vivo assessment, we first demonstrated the high oxygen affinity in vitro and great biocompatibility of Nano-PFC. Moreover, the rESW-responsive oxygen release behavior from oxygen-saturated Nano-PFC was also successfully verified in vitro and in vivo. Importantly, the wound healing of DFUs was significantly accelerated due to improved blood microcirculation, which was a result of rESW therapy (rESWT), and the targeted release of oxygen into the wound from oxygen-loaded Nano-PFC, which was triggered by the rESW. Collectively, the oxygen-saturated Nano-PFC and rESW provide a completely new approach to treat DFUs, and this study highlights the advantages of combining nanotechnology with rESW in therapeutics.

Although radial extracorporeal shock wave therapy (rESWT) has been widely used to treat orthopedic disorders with promising clinical results, rESWT largely relies on clinicians' personal experiences and arbitrary judgments, without knowing relationships between administration doses and effective doses at target sites. In fact, practitioners lack a general and reliable way to assess propagation and distribution of pressure waves inside biological tissues quantitatively. This study develops a methodology to combine experimental measurements and computational simulations to obtain pressure fields from rESWT through calibrating and validating computational models with experimental measurements. Wave pressures at the bottom of a petri dish and inside biological tissues are measured, respectively, by attaching and implanting flexible membrane sensors. Detailed wave dynamics are simulated through explicit finite element analyses. The data decipher that waves from rESWT radiate directionally and can be modeled as acoustic waves generated from a vibrating circular piston. Models are thus established to correlate pressure amplitudes at the bottom of petri dishes and in the axial direction of biological tissues. Additionally, a pilot simulation upon rESWT for human lumbar reveals a detailed and realistic pressure field mapping. This study will open a new avenue of personalized treatment planning and mechanism research for rESWT.