title: Engineered disc-like angle-ply structures for intervertebral disc replacement.
abstract: METHODS
  To develop a construction algorithm in which electrospun nanofibrous scaffolds are coupled with a biocompatible hydrogel to engineer a mesenchymal stem cell (MSC)-based disc replacement.
  
  
  OBJECTIVE
  To engineer a disc-like angle-ply structure (DAPS) that replicates the multiscale architecture of the intervertebral disc.
  
  
  BACKGROUND
  Successful engineering of a replacement for the intervertebral disc requires replication of its mechanical function and anatomic form. Despite many attempts to engineer a replacement for ailing and degenerated discs, no prior study has replicated the multiscale hierarchical architecture of the native disc, and very few have assessed the mechanical function of formed neo-tissues.
  
  
  METHODS
  A new algorithm for the construction of a disc analogue was developed, using agarose to form a central nucleus pulposus (NP) and oriented electrospun nanofibrous scaffolds to form the anulus fibrosus region (AF). Bovine MSCs were seeded into both regions and biochemical, histologic, and mechanical maturation were evaluated with in vitro culture.
  
  
  RESULTS
  We show that mechanical testing in compression and torsion, loading methods commonly used to assess disc mechanics, reveal equilibrium and time-dependent behaviors that are qualitatively similar to native tissue, although lesser in magnitude. Further, we demonstrate that cells seeded into both AF and NP regions adopt distinct morphologies that mirror those seen in native tissue, and that, in the AF region, this ordered community of cells deposit matrix that is organized in an angle-ply configuration. Finally, constructs demonstrate functional development with long-term in vitro culture.
  
  
  CONCLUSIONS
  These findings provide a new approach for disc tissue engineering that replicates multi-scale form and function of the intervertebral disc, providing a foundation from which to build a multi-scale, biologic, anatomically and hierarchically relevant composite disc analogue for eventual disc replacement.
authors.affiliation: Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Nandan L
authors.initials: NL
authors.lastname: Nerurkar
authors.forename: Sounok
authors.initials: S
authors.lastname: Sen
authors.forename: Alice H
authors.initials: AH
authors.lastname: Huang
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Elliott
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
mesh_terms: D000465:Algorithms; D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D019245:Compressive Strength / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D051445:Fibrocartilage / Q000166:cytology / Q000502:physiology; D006801:Humans; D020100:Hydrogels / Q000627:therapeutic use; D007403:Intervertebral Disc / Q000166:cytology / Q000502:physiology; D007405:Intervertebral Disc Displacement / Q000601:surgery*; D008422:Materials Testing / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D057139:Nanofibers / Q000627:therapeutic use; D011474:Prosthesis Design / Q000379:methods*; D012685:Sepharose / Q000627:therapeutic use; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000592:standards / Q000639:trends*; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D020100:Hydrogels; D012685:Sepharose