Artificial Plateletoids Recruit Blood Proteins to Shield Symbiotic Thrombin: a Silk Fibroin/Calcium Interface Medicated Thrombin Generation and Preservation

Abstract Breaking the constraints of thrombin during storage and in vivo applications remains challenging because of its low stability and sensitivity to environmental temperature and acidity. Herein, an artificial plateletoid is developed for in situ thrombin generation through a co‐incubation approach with plasma in vitro, utilizing a silk fibroin/Ca²⁺ interface, to enhance the activity and stability of the generated thrombin. Notably, the enzymatic activity of the plateletoid thrombin platform is as high as 30 U g⁻¹, leading to rapid clotting within 55 s, and it persisted for at least 90 days at as high as 37 °C. This considerably lessens the difficulties associated with maintaining the cold chain while storing and shipping thrombin formulations. Additionally, a gastric bleeding model confirmed that the plateletoid platform improved the acid resistance of thrombin by upregulating the pH of the gastric environment (pH 0.8), facilitating oral delivery of thrombin for effective hemorrhage control in highly acidic stomach conditions. This pioneering study addresses the constraints of thrombin in storage and in vivo applications and may provide a basis for further research on biological storage and delivery approaches.