Development and functional evaluation of recombinant type III collagen intrauterine implant gel.

Abstract

Intrauterine adhesion (IUA) is a prevalent complication arising from uterine surgery, significantly impacting women's fertility and overall quality of life. The conventional clinical approach involves hysteroscopic separation of uterine adhesions, though this method poses operational challenges and carries risks of postoperative re-adhesion. Alternatively, the intraoperative placement of intrauterine devices or support balloons can act as a physical barrier to prevent adhesion formation. However, its effectiveness is limited and it may result in secondary damage to the endothelial tissue. To tackle these challenges, we have engineered a temperature-responsive hydrogel incorporating Pluronic HP407/HP188 pharmaceutical excipients and recombinant type III collagen (rCol III) as a bioactive element. Upon in situ injection into the uterine cavity, this hydrogel transitions from a sol-gel phase to a gel in response to body temperature changes, thereby minimizing nonspecific distribution and prolonging the duration of treatment. In vitro studies demonstrate that rCol III temperature-responsive hydrogels exhibit favorable biocompatibility, exhibit a recruitment effect on human endometrial stromal cells, suppress the expression of the fibrotic factor transforming growth factor beta 1 and promote angiogenesis. To evaluate its efficacy in preventing IUA via in vivo experiments, we employed sexually mature female rats for IUA modeling and compared its performance with a commercially available product, cross-linked sodium hyaluronate gel. The results indicate that rCol III temperature-responsive hydrogels significantly enhance retention at the injury site, substantially promote endometrial regeneration, augment endometrial blood supply and reduce abnormal fibrin deposition. This study suggests that rCol III temperature-responsive hydrogels can effectively prevent post-surgical uterine adhesions, highlighting their potential as a promising adhesion prevention strategy.