Application of Bioactive Hydrogels for Functional Treatment of Intrauterine Adhesion

Abstract

Intrauterine adhesion (IUA) is a common endometrial disease and one of the main causes of infertility in women of childbearing age. Current treatment strategies, such as hysteroscopic adhesion resection, hysteroscopic transcervical resection of adhesion (TCRA), the use of local hormone drugs, and anti-adhesion scaffold implantation, do not provide a satisfactory pregnancy outcome for moderate-severe IUA, which presents a great challenge in reproductive medicine. With the development of material engineering, various bioactive and functional hydrogels have been developed using natural and synthetic biomaterials. These hydrogels are not only used as barely physical barriers but are also designed as vectors of hormone drugs, growth factors, and stem cells. These characteristics give bioactive hydrogels potentially important roles in the prevention and treatment of IUA. However, there is still no systematic review or consensus on the current advances and future research direction in this field. Herein, we review recent advances in bioactive hydrogels as physical anti-adhesion barriers, in situ drug delivery systems, and 3D cell delivery and culture systems for seeded cells in IUA treatment. In addition, current limitations and future perspectives are presented for further research guidance, which may provide a comprehensive understanding of the application of bioactive hydrogels in intrauterine adhesion treatment.

Research progress of stem cell therapy for endometrial injury

“…Therefore, the application of hydrogels needs to meet the following requirements: First, the size and shape of hydrogels can be adjusted to suit different uterine cavities. Second, it is easily degraded or absorbed naturally and remains in the uterine cavity long enough for treatment [ 111 ]. Moreover, temperature-responsive hydrogels exhibited better performance, responding rapidly to physical and chemical changes for the attachment of stem cells and preventing their rapid outflow from uterine cavity.…”

“…Many kinds of polymer-based hydrogels have been studied and even used for IUA treatment ( Fig. 4 ) [ 111 ]. Pluronic F-127, a Food and Drug Administration (FDA)-approved synthetic polymer with the advantages of low toxicity, biocompatibility, and thermal reversibility, can form hydrogels at physiological temperatures [ 113 ].…”

Recent progress of Bioinspired Hydrogel-based delivery system for endometrial repair

“…Hydrogels have unique properties that make them enable for application in regenerative medicine. These properties include excellent biocompatibility and biodegradability, strong water-binding capacity, which enables them to double their size while swelling, an ability to incorporate therapeutic components for controlled release as well as, the ability to encapsulate seed cells at optimum physiological conditions (Wang et al, 2021). For endometrial injury, hydrogels are applied as a physical anti-adhesion barrier and as a delivery mechanism for therapeutics.…”

Recent Developments in Biomaterial-Based Hydrogel as the Delivery System for Repairing Endometrial Injury

“…In the available reports, the mechanical strength of some hydrogel materials is so poor that they cannot provide sufficient mechanical support and even shift in position after implantation ( Wang et al, 2021 ). And in situ biomaterial-based hydrogels with non-cytotoxic degradation byproducts, minimal fibrosis, and associated foreign body reactions are also critical to the application.…”

“…But the safety issues of stem cell therapy, such as tumorigenic complications caused by stem cell implantation, as well as low cell survival rate and high cost, have limited the further clinical translation of research results. The future research and development trend should be to prepare a multifunctional hydrogel delivery system for repairing endometrial damage, which can not only provide sufficient support for the formation of the uterine cavity but also can accurately and efficiently respond to various exogenous or endogenous trigger modes at the same time, it can carry a variety of therapeutic agents with the stable and sustained release ( Lin et al, 2020 ; Wang et al, 2021 ).…”