title: Phenotypic stability, matrix elaboration and functional maturation of nucleus pulposus cells encapsulated in photocrosslinkable hyaluronic acid hydrogels.
abstract: Degradation of the nucleus pulposus (NP) is an early hallmark of intervertebral disc degeneration. The capacity for endogenous regeneration in the NP is limited due to the low cellularity and poor nutrient and vascular supply. Towards restoring the NP, a number of biomaterials have been explored for cell delivery. These materials must support the NP cell phenotype while promoting the elaboration of an NP-like extracellular matrix in the shortest possible time. Our previous work with chondrocytes and mesenchymal stem cells demonstrated that hydrogels based on hyaluronic acid (HA) are effective at promoting matrix production and the development of functional material properties. However, this material has not been evaluated in the context of NP cells. Therefore, to test this material for NP regeneration, bovine NP cells were encapsulated in 1%w/vol HA hydrogels at either a low seeding density (20×10(6)cellsml(-1)) or a high seeding density (60×10(6)cellsml(-1)), and constructs were cultured over an 8week period. These NP cell-laden HA hydrogels showed functional matrix accumulation, with increasing matrix content and mechanical properties with time in culture at both seeding densities. Furthermore, encapsulated cells showed NP-specific gene expression profiles that were significantly higher than expanded NP cells prior to encapsulation, suggesting a restoration of phenotype. Interestingly, these levels were higher at the lower seeding density compared to the higher seeding density. These findings support the use of HA-based hydrogels for NP tissue engineering and cellular therapies directed at restoration or replacement of the endogenous NP.
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 A222, Philadelphia, PA 19104, 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 A222, Philadelphia, PA 19104, USA; Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, 220 South 33rd Street, 229 Towne Building, Philadelphia, PA 19104-6315, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Martin
authors.affiliation: Department of Biomedical Engineering, University of Delaware, 150 Academy Street, Room 161 Colburn Laboratory, 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; Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, 3900 Woodland Avenue, Building 21, Room A222, 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 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 A222, Philadelphia, PA 19104, 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. Electronic address: lemauck@mail.med.upenn.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
mesh_terms: D000818:Animals; D002417:Cattle; D017931:DNA Primers; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels; D007403:Intervertebral Disc / Q000502:physiology*; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D020100:Hydrogels; D006820:Hyaluronic Acid
keywords: Cell therapy; Intervertebral disc degeneration; Mechanical properties; Three-dimensional culture; Tissue engineering