title: Translation of an engineered nanofibrous disc-like angle-ply structure for intervertebral disc replacement in a small animal model.
abstract: Intervertebral disc degeneration has been implicated in the etiology of low back pain; however, the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF) and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(ε-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, can achieve functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle-ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilized the motion segment via external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the peri-implant space and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements.
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, McKay Orthopaedic Research Laboratory, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA; Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, 220 South 33rd Street, 229 Towne Building, Philadelphia, PA 19104-6315, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, 3900 Woodland Avenue, Building 21, Room A200, Philadelphia, PA 19104, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Martin
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, McKay Orthopaedic Research Laboratory, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, 3900 Woodland Avenue, Building 21, Room A200, Philadelphia, PA 19104, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Milby
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, McKay Orthopaedic Research Laboratory, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, 3900 Woodland Avenue, Building 21, Room A200, Philadelphia, PA 19104, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Chiaro
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, McKay Orthopaedic Research Laboratory, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA.
authors.forename: Dong Hwa
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, McKay Orthopaedic Research Laboratory, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, 3900 Woodland Avenue, Building 21, Room A200, Philadelphia, PA 19104, USA.
authors.forename: Nader M
authors.initials: NM
authors.lastname: Hebela
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, McKay Orthopaedic Research Laboratory, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, 3900 Woodland Avenue, Building 21, Room A200, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania, 3400 Spruce Street, 3rd Floor, Silverstein Pavilion, Philadelphia, PA 19104, USA.
authors.forename: Lachlan J
authors.initials: LJ
authors.lastname: Smith
authors.affiliation: Department of Biomedical Engineering, University of Delaware, 125 E. Delaware Avenue, Newark, DE 19716, USA.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Elliott
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, McKay Orthopaedic Research Laboratory, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA; Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, 220 South 33rd Street, 229 Towne Building, Philadelphia, PA 19104-6315, USA; Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Suite 240, Skirkanich Hall, Philadelphia, PA 19104-6321, USA; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, 3900 Woodland Avenue, Building 21, Room A200, Philadelphia, PA 19104, USA. Electronic address: lemauck@mail.med.upenn.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
mesh_terms: D000818:Animals; D007403:Intervertebral Disc / Q000601:surgery*; D008297:Male; D023421:Models, Animal; D057139:Nanofibers; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering
keywords: Electrospinning; External fixation; Intervertebral disc; Surgical model; Tissue engineering