title: The promotion of functional urinary bladder regeneration using anti-inflammatory nanofibers.
abstract: Current attempts at tissue regeneration utilizing synthetic and decellularized biologic-based materials have typically been met in part by innate immune responses in the form of a robust inflammatory reaction at the site of implantation or grafting. This can ultimately lead to tissue fibrosis with direct negative impact on tissue growth, development, and function. In order to temper the innate inflammatory response, anti-inflammatory signals were incorporated through display on self-assembling peptide nanofibers to promote tissue healing and subsequent graft compliance throughout the regenerative process. Utilizing an established urinary bladder augmentation model, the highly pro-inflammatory biologic scaffold (decellularized small intestinal submucosa) was treated with anti-inflammatory peptide amphiphiles (AIF-PAs) or control peptide amphiphiles and used for augmentation. Significant regenerative advantages of the AIF-PAs were observed including potent angiogenic responses, limited tissue collagen accumulation, and the modulation of macrophage and neutrophil responses in regenerated bladder tissue. Upon further characterization, a reduction in the levels of M2 macrophages was observed, but not in M1 macrophages in control groups, while treatment groups exhibited decreased levels of M1 macrophages and stabilized levels of M2 macrophages. Pro-inflammatory cytokine production was decreased while anti-inflammatory cytokines were up-regulated in treatment groups. This resulted in far fewer incidences of tissue granuloma and bladder stone formation. Finally, functional urinary bladder testing revealed greater bladder compliance and similar capacities in groups treated with AIF-PAs. Data demonstrate that AIF-PAs can alleviate galvanic innate immune responses and provide a highly conducive regenerative milieu that may be applicable in a variety of clinical settings.
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL 60614, USA.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Bury
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL 60614, USA.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Fuller
authors.affiliation: Northwestern University, Evanston, IL 60208, USA.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Meisner
authors.affiliation: Northwestern University Feinberg School of Medicine, Department of Urology, Chicago, IL 60611, USA.
authors.forename: Matthias D
authors.initials: MD
authors.lastname: Hofer
authors.affiliation: Northwestern University, Institute for BioNanotechnology in Medicine (IBNAM), Chicago, IL 60611, USA; Department of Biomedical Engineering, Evanston, IL 60208, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Webber
authors.affiliation: Imperial College London, Royal School of Mines, Department of Materials and Institute for Biomedical Engineering, London, UK.
authors.forename: Lesley W
authors.initials: LW
authors.lastname: Chow
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL 60614, USA.
authors.forename: Sheba
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL 60614, USA.
authors.forename: Hatim
authors.initials: H
authors.lastname: Thaker
authors.affiliation: Northwestern University, Institute for BioNanotechnology in Medicine (IBNAM), Chicago, IL 60611, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yue
authors.affiliation: Department of Urology, Loyola University Health System, Maywood, IL 60153, USA.
authors.forename: Vani S
authors.initials: VS
authors.lastname: Menon
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL 60614, USA.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Diaz
authors.affiliation: Northwestern University, Institute for BioNanotechnology in Medicine (IBNAM), Chicago, IL 60611, USA; Northwestern University, Department of Materials Science and Engineering, Evanston, IL 60208, USA; Northwestern University, Department of Chemical and Biological Engineering, Evanston, IL 60208, USA; Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, IL 60611, USA.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Stupp
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL 60614, USA; Northwestern University Feinberg School of Medicine, Department of Urology, Chicago, IL 60611, USA; Northwestern University, Institute for BioNanotechnology in Medicine (IBNAM), Chicago, IL 60611, USA.
authors.forename: Earl Y
authors.initials: EY
authors.lastname: Cheng
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL 60614, USA; Northwestern University Feinberg School of Medicine, Department of Urology, Chicago, IL 60611, USA; Northwestern University, Institute for BioNanotechnology in Medicine (IBNAM), Chicago, IL 60611, USA; Department of Biomedical Engineering, Evanston, IL 60208, USA. Electronic address: arun-sharma@northwestern.edu.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007413:Intestinal Mucosa; D007421:Intestine, Small; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D057139:Nanofibers / Q000737:chemistry*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D051381:Rats; D011923:Rats, Nude; D012038:Regeneration / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000893:Anti-Inflammatory Agents
keywords: Angiogenesis; Bladder tissue engineering; Inflammation; Self-assembly; Urinary tract; Wound healing