Facet-Controlled Synthesis of Nanoporous Metal–Organic Frameworks for Enhanced Activity of Surface-Immobilized Thrombin

Thrombin is central to the process of the coagulation cascade reaction, and its activity directly affects fibrin formation and final hemostasis. Nanomaterial-based hemostatic agents have exhibited excellent performance in hemorrhage management. The unique exposed crystal facets of nanomaterials play a crucial role in catalytic reactions but are often overlooked. Here, a series of nanoscale zeolitic imidazolate frameworks (denoted as ZIF-8/C with exposed (100) facet, ZIF-8/TRD with mixed exposed (100) and (110) facets, and ZIF-8/RD with exposed (110) facet) were successfully synthesized with crystal facets progressively evolving from (100) to (110), which serve as catalytic platforms to accelerate the process of the coagulation cascade reaction by modulating the activity of thrombin immobilized on their surfaces. ZIF-8/TRD exhibited a striking catalytic capacity with at least 13-fold higher levels of thrombin expression compared with natural platelet-based physiological processes. Molecular dynamics (MD) simulations revealed that the special mixed-facet environment increased substrate accessibility and exhibited a more stable active site conformation. This work focuses on the regulation of enzymatic reactions carried out on the protein corona of the host material by crystal facets, paving the way for the design of hemostatic agents with enhanced thrombin activity.