A Thermo-Sensitive and Injectable Hydrogel Derived From Decellularized Amniotic Membrane to Prevent Intrauterine Adhesion by Accelerating Endometrium Regeneration

Abstract

Objective: To investigate the effect of the injectable hydrogel generated from decellularized amniotic membrane (dAM)-gel on preventing development of intrauterine adhesion (IUA) in a rat model. Methods: The dAM-gel was developed from amniotic membrane (AM) by a process of decellularization, lyophilization, and enzyme digestion. Histological analysis, residual component determination, electronic microscopy and turbidimetric gelation kinetics analysis were performed to characterize dAM-gel. The proliferation and migration of endometrial cells on dAM-gel coated surface was examined. IUA was surgically created in rats and received dAM-gel injection immediately after wound creation. Gene profiles of epithelial cell cultured on dAM-gel coated surface was evaluated by RNA-sequencing. Results: Collagen content was retained in dAM-gel while GAG content decreased significantly compared with fresh AM (fAM). Gelation of the gel is temperature sensitive and showed a matrix concentration dependent manner. Transplantation of dAM-gel significantly reduced fibrosis of IUA with recovered uterine cavity, regenerated endometrium and increased microvascular density, along with elevated pregnancy rate compared with IUA control groups. Migration of epithelial cells was greatly promoted by dAM-gel in a surgically created wound model in uterine. By comparing the RNA-sequence data of epithelial cells that cultured on dAM-gel coated and non-coated surface, respectively, distinct gene profiles relative to cellular migration, adhesion and angiogenesis and involved signaling pathway were identified. Conclusions: The injectable dAM-gel developed from AM offers a promising option for preventing endometrial fibrosis by promotion of re-epithelialization of damaged endometrium.