title: The use of bi-layer silk fibroin scaffolds and small intestinal submucosa matrices to support bladder tissue regeneration in a rat model of spinal cord injury.
abstract: Adverse side-effects associated with enterocystoplasty for neurogenic bladder reconstruction have spawned the need for the development of alternative graft substitutes. Bi-layer silk fibroin (SF) scaffolds and small intestinal submucosa (SIS) matrices were investigated for their ability to support bladder tissue regeneration and function in a rat model of spinal cord injury (SCI). Bladder augmentation was performed with each scaffold configuration in SCI animals for 10 wk of implantation and compared to non-augmented control groups (normal and SCI alone). Animals subjected to SCI alone exhibited a 72% survival rate (13/18) while SCI rats receiving SIS and bi-layer SF scaffolds displayed respective survival rates of 83% (10/12) and 75% (9/12) over the course of the study period. Histological (Masson's trichrome analysis) and immunohistochemical (IHC) evaluations demonstrated both implant groups supported de novo formation of smooth muscle layers with contractile protein expression [α-smooth muscle actin (α-SMA) and SM22α] as well as maturation of multi-layer urothelia expressing cytokeratin (CK) and uroplakin 3A proteins. Histomorphometric analysis revealed bi-layer SF and SIS scaffolds respectively reconstituted 64% and 56% of the level of α-SMA+ smooth muscle bundles present in SCI-alone controls, while similar degrees of CK+ urothelium across all experimental groups were detected. Parallel evaluations showed similar degrees of vascular area and synaptophysin+ boutons in all regenerated tissues compared to SCI-alone controls. In addition, improvements in certain urodynamic parameters in SCI animals, such as decreased peak intravesical pressure, following implantation with both matrix configurations were also observed. The data presented in this study detail the ability of acellular SIS and bi-layer SF scaffolds to support formation of innervated, vascularized smooth muscle and urothelial tissues in a neurogenic bladder model.
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Yeun Goo
authors.initials: YG
authors.lastname: Chung
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Khalid
authors.initials: K
authors.lastname: Algarrahi
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Franck
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Duong D
authors.initials: DD
authors.lastname: Tu
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rosalyn M
authors.initials: RM
authors.lastname: Adam
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA. Electronic address: carlos.estrada@childrens.harvard.edu.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Estrada
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA. Electronic address: joshua.mauney@childrens.harvard.edu.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Mauney
mesh_terms: D000818:Animals; D005260:Female; D005349:Fibroins / Q000737:chemistry*; D007413:Intestinal Mucosa / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013119:Spinal Cord Injuries / Q000601:surgery*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D001743:Urinary Bladder / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D005349:Fibroins
keywords: Bladder tissue engineering; Silk; Small intestine submucosa; Urinary tract