Efficient expansion and CRISPR-Cas9-mediated gene correction of patient-derived hepatocytes for treatment of inherited liver diseases.

Cell-based ex vivo gene therapy in solid organs, especially the liver, has proven technically challenging. Here, we report a feasible strategy for the clinical application of hepatocyte therapy. We first generated high-quality autologous hepatocytes through the large-scale expansion of patient-derived hepatocytes. Moreover, the proliferating patient-derived hepatocytes, together with the AAV2.7m8 variant identified through screening, enabled CRISPR-Cas9-mediated targeted integration efficiently, achieving functional correction of pathogenic mutations in FAH or OTC. Importantly, these edited hepatocytes repopulated the injured mouse liver at high repopulation levels and underwent maturation, successfully treating mice with tyrosinemia following transplantation. Our study combines ex vivo large-scale cell expansion and gene editing in patient-derived transplantable hepatocytes, which holds potential for treating human liver diseases.

Laser Shock Peening: Fundamentals and Mechanisms of Metallic Material Wear Resistance Improvement.

With the rapid development of the advanced manufacturing industry, equipment requirements are becoming increasingly stringent. Since metallic materials often present failure problems resulting from wear due to extreme service conditions, researchers have developed various methods to improve their properties. Laser shock peening (LSP) is a highly efficacious mechanical surface modification technique utilized to enhance the microstructure of the near-surface layer of metallic materials, which improves mechanical properties such as wear resistance and solves failure problems. In this work, we summarize the fundamental principles of LSP and laser-induced plasma shock waves, along with the development of this technique. In addition, exemplary cases of LSP treatment used for wear resistance improvement in metallic materials of various nature, including conventional metallic materials, laser additively manufactured parts, and laser cladding coatings, are outlined in detail. We further discuss the mechanism by which the microhardness enhancement, grain refinement, and beneficial residual stress are imparted to metallic materials by using LSP treatment, resulting in a significant improvement in wear resistance. This work serves as an important reference for researchers to further explore the fundamentals and the metallic material wear resistance enhancement mechanism of LSP.