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High‐grade serous tubo‐ovarian cancer (HGSTOC) is an aggressive gynecological malignancy including homologous recombination deficient (HRD) and homologous recombination proficient (HRP) groups. Despite the therapeutic potential of poly (ADP‐ribose) polymerase inhibitors (PARPis) and anti‐PDCD1 antibodies, acquired resistance in HRD and suboptimal response in HRP patients necessitate more precise treatment. Herein, single‐cell RNA and single‐cell T‐cell receptor sequencing on 5 HRD and 3 HRP tumors are performed to decipher the heterogeneous tumor immune microenvironment (TIME), along with multiplex immunohistochemistry staining and animal experiments for validation. HRD tumors are enriched with immunogenic epithelial cells, FGFR1+PDGFRβ+ myCAFs, M1 macrophages, tumor reactive CD8+/CD4+ Tregs, whereas HRP tumors are enriched with HDAC1‐expressing epithelial cells, indolent CAFs, M2 macrophages, and bystander CD4+/CD8+ T cells. Significantly, customized therapies are proposed. For HRD patients, targeting FGFR1+PDGFRβ+ myCAFs via tyrosine kinase inhibitors, targeting Tregs via anti‐CCR8 antibodies/TNFRSF4 stimulation, and targeting CXCL13+ exhausted T cells by blocking PDCD1/CTLA‐4/LAG‐3/TIGIT are proposed. For HRP patients, targeting indolent CAFs, targeting M2 macrophages via CSF‐1/CSF‐1R inhibitors, targeting bystander T cells via tumor vaccines, and targeting epithelial cells via HDAC inhibitors. The study provides comprehensive insights into HRD and HRP TIME and tailored therapeutic approaches, addressing the challenges of PARPi‐resistant HRD and refractory HRP tumors. [ABSTRACT FROM AUTHOR]

Reproductive health concerns like Mayer‐Rokitansky‐Küster‐Hauser (MRKH) syndrome are prevalent in today's society. MRKH syndrome is a condition that severely affects women's sexual life, fertility, and mental health and has a high prevalence of one out of 5000 female births. Vaginoplasty is the primary method to regain patients' reproductive health. However, conventional vaginoplasty faces various challenges, including complex and non‐customized treatment procedures causing intense pains and complications. To bring new advances to vaginoplasty, a 3D‐printed hydrogel scaffold is developed to provide satisfactory mechanical support and bioactivity for accelerating defect repair after surgery. The hydrogel scaffold consisting of gelatin methacryloyl (gelMA) and carrageenan (Car) is custom 3D‐printed using an ambient temperature printing system. Furthermore, the scaffold undergoes dual‐crosslinking through chemical crosslinking of gelMA and ionic crosslinking of Car with magnesium ions (Mg2+). This dual‐crosslinking strategy substantially improves the overall mechanical properties of the scaffold and introduces bioactive Mg2+. The sustained release of Mg2+ plus the extracts from the dual‐crosslinked scaffold significantly promotes cell proliferation, migration and angiogenesis. In a preclinical rat model with penetrating genital tract defects mimicking vaginoplasty, the implantation of dual‐crosslinked scaffold repairs the penetrating wounds to near‐normal levels within one week, showing potential as an alternative for better regaining reproductive health. [ABSTRACT FROM AUTHOR]