Cross-linked recombinant type III collagen hydrogel for prevention of intrauterine adhesions

Intrauterine adhesions (IUA) are primarily caused by damage to the basal layer of the endometrium during uterine surgery. Hysteroscopic adhesiolysis is the treatment of choice; however, recurrent adhesions following surgery often require management with physical barriers. These barriers, however, are insufficiently effective and may cause endometrial damage, thereby hindering tissue regeneration. In this study, a cross-linked recombinant type III collagen hydrogel (CRC) was developed using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as cross-linking agents, a material capable of forming an in situ barrier within the damaged uterine cavity to isolate the wound site. Its three-dimensional interconnected network creates a microenvironment conducive to endometrial regeneration: the hydrogel exhibits excellent biocompatibility, maintains the viability of endometrial stromal cells, promotes cell recruitment and angiogenesis, and inhibits the expression of the pro-fibrotic cytokine TGF-β1. Furthermore, in a rat IUA model, the hydrogel prolonged wound retention time, significantly enhanced the recovery of endometrial gland density and thickness, improved uterine blood perfusion, and reduced abnormal fibrin deposition. In summary, the cross-linked recombinant type III collagen hydrogel is an ideal candidate material that combines the dual functions of physical isolation and regenerative repair, and can be used for the prevention and treatment of postoperative IUA.