Temperature-sensitive hydrogel loaded with DNase I alleviates epidural fibrosis in a mouse model of laminectomy

Excessive epidural fibrosis attached to the dura mater is the major cause of recurrent failed back surgery syndrome after spine surgery. Neutrophil extracellular traps (NETs) promote epidural fibrosis, raising the possibility that the DNA backbone of NETs may be a potential target in the therapy of epidural fibrosis. Human body temperature-sensitive hydroxypropyl chitin hydrogel solutions were prepared to encapsulate DNase I, which gradually decomposed in vivo. DNase I, which was released from temperature-sensitive hydrogels, destroyed the DNA backbone of NETs and dispersed the clustering of myeloperoxidase (MPO) in NETs. Evidence from MRI, H&E and Masson staining supported that hydroxypropyl chitin hydrogels loaded with DNase I were nontoxic and reduced epidural fibrosis. As expected, fibronectin in the wound was significantly abridged in the mice treated with hydrogels loaded with DNase I. Compared with the gelatin sponge absorbing DNase I, temperature-sensitive hydroxypropyl chitin hydrogels loaded with DNase I were more powerful in the therapy of epidural fibrosis. These results indicate that temperature-sensitive hydroxypropyl chitin hydrogels were effective in DNase I encapsulation and alleviation of epidural fibrosis in a mouse model of laminectomy.

Automated summary

This study reports a temperature-sensitive hydroxypropyl chitin hydrogel encapsulating DNase I, which effectively reduces epidural fibrosis after spine surgery. By degrading the DNA backbone of neutrophil extracellular traps (NETs) and dispersing the clustering of myeloperoxidase (MPO) in NETs, the hydrogels loaded with DNase I demonstrated a significant decrease in fibronectin accumulation in the wound.