| Summary: | Abstract Uterine abnormalities infertility can be treated with implantable patches for tension‐free healing. However, the existing clinical patches are still limited in effective uterus recovery, resulting in low pregnancy and live birth rates. Herein, a novel engineered, and biocompatible Janus collagen patch (JCOP) is developed to achieve excellent uterine defect recovery and increase effective live births. The JCOP can highly match the structure, micromorphology, and mechanical properties of a natural uterus due to homologous‐like tissue homogeneity. JCOP's rough surface and loose‐extracellular‐matrix‐like porosity promote fibroblast adhesion and tissue regeneration, whereas its smooth surface reduces fibroblast adhesion and prevents visceral adhesions. Additionally, it exhibits exceptional resistance to swelling and deformation along with stable mechanical strength for long‐term preservation in the body and can withstand the highest uterine pressure in a humid interior environment attributed to its superior structural layout. Moreover, JCOP@bF, a functional JCOP linked to basic fibroblast growth factor (bFGF) via a specific collagen‐binding domain, significantly promotes repair of the injured uterus, restores the ability of the endometrium to accept embryos, and supports their development to a viable stage in a rat model of uterine damage. This study shows great promise for treating infertility caused by uterine damage.
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