Significance: Nanoparticle-mediated delivery of siRNA to hepatocytes has treated disease in humans. However, systemically delivering RNA drugs to nonliver tissues remains an important challenge. To increase the number of nanoparticles that could be studied in vivo, we designed a high-throughput method to measure how >100 nanoparticles delivered mRNA that was translated into functional protein in vivo. We quantified how >250 lipid nanoparticles (LNPs) delivered mRNA in vivo, identifying two LNPs that deliver mRNA to endothelial cells. One of the LNPs codelivered Cas9 mRNA and single-guide RNA in vivo, leading to endothelial cell gene editing. This approach can identify nanoparticles that target new cells.

Recent advances in nanomaterials and nano-microfabrication have enabled the development of flexible wearable electronics. However, existing manufacturing methods still rely on a multi-step, error-prone complex process that requires a costly cleanroom facility. Here, we report a new class of additive nanomanufacturing of functional materials that enables a wireless, multilayered, seamlessly interconnected, and flexible hybrid electronic system. All-printed electronics, incorporating machine learning, offers multi-class and versatile human-machine interfaces. One of the key technological advancements is the use of a functionalized conductive graphene with enhanced biocompatibility, anti-oxidation, and solderability, which allows a wireless flexible circuit. The high-aspect ratio graphene offers gel-free, high-fidelity recording of muscle activities. The performance of the printed electronics is demonstrated by using real-time control of external systems via electromyograms. Anatomical study with deep learning-embedded electrophysiology mapping allows for an optimal selection of three channels to capture all finger motions with an accuracy of about 99% for seven classes.

Synthetic designer matrix enhances muscle stem cell function and engraftment in injured dystrophic and aged skeletal muscles.

Significance: Skeletal muscle is one of the largest tissues in the body and can regenerate when damaged through a population of resident muscle stem cells. A type of muscle trauma called volumetric muscle loss overwhelms the regenerative capacity of muscle stem cells and engenders fibrotic supplantation. A comparison of muscle injuries resulting in regeneration or fibrosis revealed that intercellular communication between neutrophils and natural killer cells impacts muscle stem cell-mediated repair. Perturbation of neutrophil–natural killer cell interactions resulted in a variation of healing outcomes and suggested that immunomodulatory interventions can be effective to prevent aberrant healing outcomes.