Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders.

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.

Engineering a biomimetic bone scaffold that can regulate redox homeostasis and promote osteogenesis to repair large bone defects.

The reconstruction of a large bone defect to an extent that exceeds its self-healing capacity has been a great clinical challenge. In pursuit of this goal, a biomaterial-based scaffold that comprises radially aligned mineralized collagen (RA-MC) fibers that incorporate nanosilicon (RA-MC/nSi), is proposed. The chemical composition of the MC fibers is similar to that of natural bone matrices. The therapeutic efficacy of the RA-MC/nSi scaffold is evaluated in a mouse model with an experimentally created large calvarial defect. In vitro and in vivo results reveal that the RA-MC fibers of the scaffold guide the directional infiltration and migration of reparative cells from the host tissue toward the center of the defect, suggesting a potential application in promoting osteoconductivity. The incorporated nSi renders the scaffold able sustainably to release gaseous hydrogen and water-soluble silicic acid during the healing process. The released hydrogen gas can effectively regulate redox homeostasis and mitigate excessive inflammation, and the silicic acid can promote the proliferation of reparative cells and enhance their osteogenic differentiation, indicative of osteoinductivity. These findings support the use of the as-proposed biomimetic RA-MC/nSi scaffold as a promising bone substitute to enhance the regeneration of large bone defects.