Multifunctional Hydrogels Loaded with Mn Single-Atom Nanozymes: Advancing Endometrial Repair

Irregular endometrial damage often evolves into chronic conditions, such as endometrial thinning, functional tissue fibrosis, and intrauterine adhesions. These conditions pose significant challenges to female reproductive health. Addressing this, we developed a dynamic double-cross-linked hydrogel for the repair of fragile and dynamic endometrial tissue. This hydrogel integrates natural bioactive components (chitosan, protocatechuic aldehyde, and Fe(III)) and serves as a scaffold for Mn single-atom nanozymes (Mn SAN). Through dynamic covalent and hydrogen bonding, the hydrogel exhibits exceptional adhesion, injectability, degradability, and self-healing capabilities. The embedded Mn SAN, leveraging their unique metal active center, deliver superior catalytic activity and selectivity. When introduced into endometrial lesions in mice, this bioactive hydrogel exerts a synergistic effect that not only significantly boosts cell proliferation but also effectively modulates hormone levels. As a result, it facilitates remarkable tissue repair within a mere two-week period. Importantly, this therapeutic approach is both hormone- and cell-free, representing a noninvasive intervention. This innovative design thus paves the way for a groundbreaking strategy in the engineering of advanced materials specifically tailored for endometrial regeneration.