Porcine urinary bladder matrix encapsulated biological patch enhances dural repair and promotes anti-adhesion via mesothelial cell induction.

Decellularized biomaterial-based dural patches are clinically employed as dura mater substitutes, owing to their biocompatibility, biodegradability, mechanical flexibility, and efficacy in promoting tissue regeneration. However, these biological grafts have challenges related to patch durability, cerebrospinal fluid leakage, and brain tissue adhesion. In this study, we developed a composite dural patch with a biomimetic structure by encapsulating multilayered small intestinal submucosa (SIS) membranes using basement membrane-containing urinary bladder matrix (UBM) membranes as outer layers, to enhance dural repair. The newly designed UBM@SIS patch demonstrates superior mechanical properties, excellent tissue regeneration capabilities, and enhanced anti-adhesion effects. Immunofluorescent staining revealed a densely organized cell layer anchored to the surface of the UBM@SIS patch, identified as mesothelial cells (Pan-Cytokeratin+/E-cadherin+) and arachnoid barrier cells (ABCs), which are essential for lubricating brain tissue, preventing adhesion, and reducing cerebrospinal fluid leakage. In contrast, only a sparse presence of Pan-Cytokeratin-labeled mesothelial cells and E-cadherin-labeled ABCs was observed on the SIS patch, exhibiting incomplete pia mater and significant adhesion on interface between patch and brain tissue. Furthermore, neurotoxicity evaluations confirmed that the encapsulation of UBM reduces astrogliosis and neuroinflammatory response in early stage. These results suggest that the novel UBM@SIS patch effectively addresses the limitations of existing biological patches and holds significant potential for clinical application.