Hydrophobic Polystyrene-Modified Gelatin Enhances Fast Hemostasis and Tissue Regeneration in Traumatic Brain Injury

Hemostatic sealant is required to deal with blood loss, especially in the scenario of traumatic brain injury (TBI), which presents high rates of morbidity and disability. Hemostasis in surgery with traditional gelatin-based sealants often leads to blood loss and other issues in brain because of the hydrophilic gelatin swelling. Herein, hydrophobic effects on the hemostasis in TBI surgery are studied by tuning the chain length of polystyrene (PS) onto methylacrylated gelatin (Gel-MA). The hydrophobicity and hemostatic efficiency can be tuned by controlling the length of PS groups. The platelet activation of modified sealants Gel-MA-2P, Gel-MA-P, and Gel-MA-0.5P is as much as 17.5, 9.1, and 2.1 times higher than Gel-MA in vitro. The hemostatic time of Gel-MA-2P, Gel-MA-P, and Gel-MA-0.5P groups is 2.0-, 1.6-, and 1.1-folds faster than that in Gel-MA group in TBI mice. Increased formation of fibrins and platelet aggregation can also be observed in vitro by scanning electron microscopy. Animal's mortality is lowered by 46%, neurologic deficiency is reduced by 1.5 times, and brain edema is attenuated by 10%. Protein expression is further investigated to exhibit toxic iron-related processes caused by delayed hemostasis and activation of platelets via PI3K/PKC-α signaling. The hydrophobic Gel-MA has the potential in hemostatic TBI and promotes nervous system recovery in brain with the potentials in clinics.