New Frontiers in Urinary Tract Reconstruction: A Tissue Engineered Nanofiber Fibrinogen Matrix in a Human Model

Michael C McManus, Eugene D Boland*, Gary L Bowlin*, David G Simpson*, Paul G Espy, Harry P Koo
Virginia Commonwealth University, Richmond, VA

Introduction: A major challenge in urologic surgery is urinary tract reconstruction. There are no commercially available tissue engineered products that adequately replace autologous tissue. Electrospinning uses charge separation to produce micro- to nanoscale non-woven fibrous mats capable of mimicking native ECM. Our objective is to demonstrate that human bladder smooth muscle cells (BSM) remodel electrospun fibrinogen mats.
Methods: Fibrinogen scaffolds were electrospun and disinfected using standard methods. Scaffolds were seeded with 5x10⁴ BSM per scaffold. Cultures were supplemented with aprotinin concentrations of 0 KIU/ml (no aprotinin), 100 KIU/ml or 1000 KIU/ml and incubated with twice weekly media changes. Samples were removed for testing at 1, 3, 7 and 14 days. Cultured scaffolds were evaluated using WST-1 cell proliferation assay, scanning electron microscopy and trichrome staining.
Results: Cell seeding and culture demonstrated that human BSM readily migrated into and remodeled electrospun fibrinogen scaffolds with deposition of collagen fibrils. Proliferation was suppressed, with respect to a 2-D control, during the initial cell migration phase. Histology confirmed that proliferation increased during the later stages of remodeling. Remodeling was slower at higher aprotinin concentrations.
Conclusions: These results demonstrate that human BSM rapidly remodel an electrospun fibrinogen scaffold and deposit native collagen fibrils. The process can be modulated using aprotinin, a protease inhibitor. There is tremendous potential for electrospun fibrinogen as a urologic tissue engineering scaffold in a human model. While there is still much work to be done, these initial findings indicate that fibrinogen scaffolds deserve further investigation for use in urologic tissue engineering.

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