Hydrogen‐Bonded Organic Framework (HOF)‐Based Single‐Neural Stem Cell Encapsulation and Transplantation to Remodel Impaired Neural Networks

Abstract Herein we present a new way to encapsulate neural stem cells (NSCs) by using hydrogen‐bonded organic frameworks (HOFs) to overcome the common causes of low therapeutic efficacy during NSC transplantation: 1) loss of fundamental stem cell properties, “stemness”, before transplantation, 2) cytomembrane damage during transplantation, and 3) apoptosis due to oxidative stress after transplantation. Porous carbon nanospheres (PCNs) are doped into the HOF shell during the process of mineralization to endow the cellular exoskeletons with hierarchical hydrogen bonds, and the ability to resist oxidative stress due to the catalase and superoxide dismutase‐like activities of PCN. Under NIR‐II irradiation, thermal‐responsive hydrogen bonds dissociate to release NSCs. Stereotactic transplanting encapsulated NSC into the brain of an Alzheimer's disease (AD) mouse model further verifies that our design can enhance NSC viability, promote neurogenesis, and ameliorate cognitive impairment. As the first example of using HOFs to encapsulate NSCs, this work may inspire the design of HOF‐based exoskeletons to ameliorate neurogenesis and cognitive behavioral symptoms associated with AD.