Shape-memory scaffold targets inflammation and fibrosis to restore endometrium and fertility in intrauterine adhesions

Intrauterine adhesion (IUA) is a major cause of infertility, yet current treatments remain limited in preventing fibrosis and restoring functional endometrium. We report a bi-drug, bifunctional, biodegradable shape-memory regenerative (BiSMR) scaffold enabling minimally invasive implantation, sequential drug release, and barrier protection. Proteomic profiling of chemical, mechanical, and combined injury models revealed inflammatory activation, extracellular matrix remodeling, and impaired regenerative programs, providing a molecular rationale for combining epigallocatechin gallate (EGCG) with 17β-estradiol (E 2 ). BiSMR couples an E 2 -loaded PLTG [poly( l -lactide)- co -trimethylene carbonate- co -glycolic acid] backbone with a PDA-EGCG@HAMA coating, enabling rapid EGCG release followed by sustained E 2 delivery. In vitro, BiSMR promoted cell proliferation, migration, angiogenesis, and M2 polarization while suppressing myofibroblast transition. In rat IUA models, BiSMR restored endometrial structure and vascularization, reduced fibrosis, and improved implantation and live birth rates. Proteomics revealed down-regulation of fibrosis- and inflammation-related effectors and restoration of protein biosynthesis and regenerative pathways. BiSMR offers a promising strategy for IUA therapy and fertility restoration.