Preparation of Fibroblast Suppressive Poly(ethylene glycol)--poly(l-phenylalanine)/Poly(ethylene glycol) Hydrogel and Its Application in Intrauterine Fibrosis Prevention.

Intrauterine adhesions (IUA) often occur as a result of trauma to the basal layer after curettage, postpartum hemorrhage, or surgical miscarriage. Endometrial fibrosis is the primary pathological feature of IUA. The characteristic features of IUA include excessive deposition and reorganization of the extracellular matrix, replacing the normal endometrium. To prevent uterine fibrosis after injury, we prepared and evaluated a type of fibroblast suppressive hydrogel. Poly(ethylene glycol)--poly(l-phenylalanine) (PEBP) copolymers were successfully synthesized by ring opening polymerization of l-Phenylalanine N-carboxyanhydride, initiated by methoxy-poly(ethylene glycol)-amine. Injectable PEBP/PEG hydrogels were subsequently formed through π-π accumulations between PEBP macromolecules and hydrogen bonds among PEBP, PEG, and HO molecules. PEBP/PEG hydrogel could suppress the proliferation of fibroblasts due to the action of l-Phe, released sustainably from PEBP/PEG gels. Lastly, the in vivo preventive effect of PEBP/PEG hydrogel on fibrosis was evaluated in a rat uterine curettage model. It was found that PEBP/PEG hydrogel suppressed uterine fibrosis caused by curettage and promoted embryo implantation in injured uterine by regulating the expression and interactions of transforming growth factor beta 1 (TGF-β1) and Muc-4. PEBP/PEG hydrogels have the potential for application in uterine adhesion prevention owing to their fibrosis preventive and pregnancy promotiing effects on uterine tissue after injury.