Dual‐Crosslinked Bioactive Hydrogel Scaffold for Accelerated Repair of Genital Tract Defect

Abstract 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 (Mg 2+ ). This dual‐crosslinking strategy substantially improves the overall mechanical properties of the scaffold and introduces bioactive Mg 2+ . The sustained release of Mg 2+ 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.