Succinic Ester-based Shape Memory Gelatin Sponge For Noncompressible Hemorrhage

Shape memory sponges are very promising in stopping the bleeding from noncompressible and narrow entrance wounds.However,few shape memory sponges have fast degradable properties in order to not hinder tissue healing.In this work,a succinate-based rapidly degradable shape memory hemostatic sponge(Ssponge)was prepared by crosslinking polymerization and freeze-drying with good biocompatibility and low cost gelatin and Bi-PEG-SS.In the process of bulk cross-linking,the succinyl ester bond is introduced,and its cyclic degradation characteristics make the sponge degrade quickly after it plays its role,without causing foreign body reaction.In order to test the degradation performance and biocompatibility of the sponge in vivo,a subcutaneous embedding experiment was designed in rats.The commercially available Csponge and Ssponge were implanted subcutaneously into the back of rats,respectively.The degradation of the sponges was monitored by MRI.The results showed that Ssponge was completely degraded at 14 days,while Csponge was still present at 21 days.The slow degradation of Csponge resulted in a severe foreign body reaction(more inflammatory cells and thicker fibrous cysts compared with Ssponge).Ssponge has the advantages of fast degradation,good biocompatibility and greater safety.In order to test the hemostatic properties of the sponge,a rat liver hemostatic experiment(transection and penetrating rat liver hemorrhage models)was performed.The results showed that Ssponge performed better in both hemostasis models with shorter hemostasis time and less blood loss than the commercially available Csponge.In this work,rat liver penetrating injury was used as a regeneration model to verify the effect of the rapid degradation property of the sponge on tissue regeneration.The results showed that the Ssponge treated wounds were basically healed at 14 days.However,due to the slow degradation of commercially available Csponge,there were still unhealed areas in the wounds treated with Csponge for 21 days.Compared with the Csponge group,the Ssponge group had lower liver injury scores and better liver healing.The H&E and Masson staining of the liver tissue showed that the Ssponge group had a larger regeneration area,more regenerated ducts,and less fibrotic areas,indicating better liver regeneration and healing in the Ssponge group.To further analyze the healing stage of the sponge-treated liver,immunofluorescence staining with anti-Ki-67 antibody and ALB antibody was performed in this work.Ki-67 is a non-histone nuclear protein that is a marker of cell proliferation in injured tissues,so the number of Ki-67-positive cells is very low in healthy liver.For albumin(ALB),only normal hepatocytes can secrete it.Immunofluorescence staining showed that there were fewer Ki-67 positive cells and more ALB in the Ssponge group than in the Csponge group,indicating better liver regeneration and healing in the Ssponge group.Since both gelatin and PEG used in this study have good CFDA and FDA histories,they have good industrialization prospects.Future studies will focus on further optimization of the performance of the system and validation of its safety and efficacy in large animals.Overall,it is shown that Ssponge,with a fast degradation behavior,is not only highly efficient in stopping bleeding,but also not detrimental for tissue healing,possessing promising clinical translational potential.