Abstract 4141626: A closed-loop system based on piezoelectric thin-film sensors and photothermal nanomaterials enables precise renal denervation for the treatment of hypertension

Background: Since renal sympathetic nerves play a crucial role in the pathogenesis of hypertension, renal denervation (RDN) has emerged as a new solution for hypertensive patients, especially those with refractory hypertension. However, clinical trials have shown inconsistent results with current RDN techniques. This may be attributed to the short duration of effects induced by nerve fiber regeneration after ablation and the lack of measures to localize and assess efficacy. Hypothesis: In this study, we attempted to construct a sustainable closed-loop RDN system and overcome these limitations. Methods: We designed a new closed-loop RDN system containing a monitoring module with piezoelectric thin-film sensor (PTFS) and an intervention module with Pd nanopartical shell (PdNPS)-mediated photothermal nerve ablation. The feasibility and safety of this closed-loop system was explored in canine models of acute and chronic renal sympathetic nerve stimulation simulating hypertension, respectively. Results: In vivo experiments showed that PTFS on the surface of the renal artery enabled monitoring and collection of arterial pulsations and blood pressure. The self-monitoring function based on PTFS can guide PdNPS to maximize RDN. During the treatment window of 90-120s, PdNPS could maintain an ablation temperature of 58-62°C under NIR irradiation to inhibit renal sympathetic nerve activity and function. In the hypertension simulation model, the increase in blood pressure was 54.65% lower in the PdNPS group compared to the control group (p<0.05). Histologic testing showed that PdNPS ablation resulted in necrosis and degeneration of the renal sympathetic nerves, whereas the renal arteries were structurally intact and functioned normally. In addition, the increase in blood pressure after 1 month was 52.84% lower in the PdNPS group compared with the sham group (p<0.05), suggesting microinjection of PdNPS photothermal ablation is sustainably effective. Conclusion: This novel closed-loop system has the potential for safe and effective RDN, which would provide a new therapeutic strategy for refractory hypertension and even chronic diseases of the autonomic nervous system.