Sustained oxygen release Organic/Inorganic composite scaffold Delivers BMSCs to promote spinal cord injury repair

The clinical repair of spinal cord injury (SCI) has long been constrained by the twin challenges of a persistent hypoxic microenvironment at the injury site and the low survival rate of transplanted cells. This study innovatively constructs a three-dimensional (3D) oxygen-releasing scaffold Poly(lactic-co-glycolic acid (PLGA)-Calcium Peroxide (CPO)/Gelatin Methacryloyl (PLGA-CPO/GelMA) featuring a core–shell structure achieved via emulsification-photocrosslinking technology. PLGA-CPO microspheres provide sustained oxygen release for over 14 days, while the GelMA hydrogel establishes a biomimetic microenvironment.   In vitro   experiments confirmed that under hypoxic conditions, the hydrogel composite scaffold maintained the proliferative activity of the bone marrow mesenchymal stem cells during 3D co-culture. Furthermore, when co-cultured with neurons in a 2D system simulating the   in vivo   SCI environment, the scaffold significantly promoted neuronal survival and proliferation. In a T9 complete transection SCI rat model, the scaffold transplantation group exhibited significantly improved Basso, Beattie, Bresnahan locomotor scores compared to control groups. Histological analysis revealed increased axonal regeneration, reduced glial scarring, and high survival rates of transplanted mesenchymal stem cells at the implantation site in the scaffold-treated group. Mechanistic studies demonstrated that the composite scaffold exerted a triple synergistic effect, encompassing promotion of angiogenesis and neural regeneration, alongside suppression of apoptotic responses.   The developed Organic/Inorganic Composite scaffold sustainably ameliorates the injury microenvironment and synergistically enhances stem cell-mediated repair efficacy, providing a promising tissue engineering solution with significant potential for clinical translation in spinal cord injury.