Multiresponsive Microcapsules for Prevention of Intrauterine Adhesion

Intrauterine adhesion (IUA) has a significant negative impact on women's reproductive health. One of the development trends of biomaterials for prevention of IUA is improving the stability and multifaceted functions. Here, we propose a multiresponsive microcapsule (A/G-Fe₃O₄-Se) with an alginate (ALG) and gelatin methacryloyl (GelMA) dual-network hydrogel shell loaded with magnetic nanoparticles (Fe₃O₄-Se) and an ultrasound-responsive decafluoropentane core for the prevention of IUA using a microfluidic technique. The microcapsules inherited the biofriendly advantages of ALG and GelMA. The encapsulated magneto-responsive Fe₃O₄-Se made the microcapsule flexibly change the distribution to adapt to the irregular shape of the uterus and better exert the therapeutic effect. Besides, the A/G-Fe₃O₄-Se microcapsules demonstrated antioxidant, antibacterial, and pro-healing properties in vitro. Moreover, in the IUA rat models, we also observed a reduction in oxidative stress, better endometrial regeneration, and improved endometrial receptivity and pregnancy rates after treatment of the microcapsules. Consequently, the A/G-Fe₃O₄-Se microcapsules can be used as a promising strategy for the treatment of damaged endometrium as well as prevention of IUA.