Early Cellular and Stromal Responses in Regeneration Versus Repair of a Mammalian Bladder Using Autologous Cell and Biodegradable Scaffold Technologies

Abstract

Internal organ regeneration holds promise for changing medical technology and decreasing organ shortages. Current medical treatment for internal organ failure is largely limited to organ transplantation. A construct composed of synthetic biopolymer with autologous cells has shown long-term clinical benefit in patients undergoing augmentation cystoplasty. However, to our knowledge early cellular and stromal events during bladder regeneration have not been elucidated. In situ cellular responses to 2 biopolymer implants, including a poly(lactic-co-glycolic acid) (Sigma-Aldrich) based biodegradable mesh scaffold with autologous urothelial and smooth muscle cells (construct) and a poly(lactic-co-glycolic acid) based biodegradable mesh scaffold alone without cells (scaffold), were compared in a canine model of augmentation cystoplasty. Healing events were correlated with urodynamic assessments. Construct implants regenerated baseline urodynamics as early as 4 months after implantation. Urodynamics following scaffold implantation failed to return to baseline by study termination at 9 months. Functional differences elicited by construct and scaffold implants correlated with structural differences in the neotissues. Construct stroma had greater vascularization with gently folded, interwoven connective tissue elements. Scaffold stroma was dense, haphazardly organized connective tissue. Urothelium regenerated in response to construct and scaffold implantation. However, only construct had normal stroma, well developed detrusor and abundant alpha-smooth muscle actin (Vector Laboratories, Burlingame, California) cell staining at early time points, leading to a structurally and functionally complete regenerated bladder wall at 9 months. Early cellular and stromal events distinguish healing processes that lead to bladder wall regeneration or repair. Construct implants containing cells elicit early healing processes that culminate with the regeneration of complete mucosal and muscular components, whereas the response to scaffold implantation is consistent with reparative healing, that is with mucosal growth but incomplete tissue layer development.