However, two hurdles are preventing extending their applications in vivo. The first one is that just as commercialized sealants, none of the reported Tetra-PEG hydrogels could be controllably removed without mechanical debridement, which is extremely dangerous because of their high mechanical strength. Besides, they possess long degradation time, which will lead to severe foreign body reactions, tissue adhesion, disturbed tissue healing, and obstruction of the circulatory system, when used in vivo. Here, to overcome the limitations of the existing ammonolysis based Tetra-PEG hydrogels, we construct an optimized one (SS) with fast degradable and controllably dissolvable properties via Tetra-PEG-NH2 and tetra-armed poly(ethylene glycol) succinimidyl succinate (Tetra-PEG-SS) . The resulting SS exhibits biocompatibility superior to the reported degradable Tetra-PEG hydrogel (SG) based on Tetra-PEG-NH2 and tetra-armed poly(ethylene glycol) succinimidyl glutarate (Tetra-PEG-SG) . More importantly, in contrast to the disappointing results of SG that leads to serious adverse effects in in vivo hemostasis due to the long retention, SS causes almost no noticeable side effects with outstanding hemostasis efficacy even under the anticoagulated situations. This hydrogel is a promising candidate for the next-generation in vivo sealants in the aged society.
