Harnessing three-dimensional porous chitosan microsphere embedded with adipose-derived stem cells to promote nerve regeneration.

BACKGROUND: Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects. METHODS: In vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats. RESULTS: Compared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration. CONCLUSIONS: The ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair.

Safety Analysis of Adverse Events of Ultrasound Contrast Agent Lumason/SonoVue in 49,100 Patients.

This study assessed the incidence of mild, moderate and severe adverse events (AEs) and examined their association with age, sex, body region examined, time to event and duration of the AE(s) in a large cohort of patients who underwent contrast-enhanced ultrasound (CEUS) with Lumason/SonoVue. In this retrospective observational study, 49,100 patients who underwent CEUS were analyzed. Forty-three (0.088%) patients experienced AEs, with 23 (0.047%) patients experiencing mild AEs, 13 (0.026%) experiencing moderate AEs and 7 (0.014%) experiencing severe AEs. No fatal event occurred. There was no age- or sex-related difference in the incidence of the AE(s) (p = 0.158 and p = 0.474). Inpatients (0.17%) more often experienced AEs than outpatients (0.06%, p = 0.003). The mean time to event for mild and moderate AEs was 14.50 ± 6.96 and 15.75 ± 10.40 min, respectively, whereas that for severe AEs was 1.89 ± 1.21 min after the injection. The remission time for mild and moderate AEs was approximately 30-40 min, and all patients with severe AEs recovered within 12 h. Twenty-one (48.8%) patients received medical treatment. In summary, Lumason/SonoVue has a good safety profile with a low incidence of AEs, most of which are mild with a short time to event and duration.