Microfluidic 3D-printed MSC-laden bioactive hydrogel for intrauterine adhesion prevention and endometrial regeneration

Increasing occurrence of intrauterine adhesion (IUA) is a serious threat to the reproductive health of women in recent years. However, treatment options remain limited. Mesenchymal stem cell (MSC)-based therapies have shown a promising regenerative capacity of injured endometrium but have limited effectiveness by the low survival duration of transplanted cells. Herein, we present a bioactive hydrogel scaffold loaded with adipose tissue-derived MSC (AT-MSC) by using a three-dimensional (3D) bioprinting technology, which combines the characteristics of the synthetic thermos-responsive material PF-127 and the natural-derived, photo-polymerizable material GelMA. The composite hydrogel scaffold shows enhanced mechanical as well as biocompatibility. In addition, the porous structure endows the 3D-printed scaffold with a favorable growing environment for MSC and increase the retention rate of cells. Finally, the dual repair effects of the MSC-laden gel scaffold on endometrial damage and regeneration are validated in a rat IUA model. This study demonstrates that the composite system could improve neovascularization, increase number of glands, and ameliorate fibrotic formation of endometrium. Thus, it is believed that such bioactive MSC-loaded scaffold is a promising candidate for prevention of IUA with reliable endometrial regeneration properties.