title: Development and validation of a bioreactor system for dynamic loading and mechanical characterization of whole human intervertebral discs in organ culture.
abstract: Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48h of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques.
authors.affiliation: Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Walter
authors.affiliation: Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Illien-Jünger
authors.affiliation: Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Nasser
authors.affiliation: Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Hecht
authors.affiliation: Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: james.iatridis@mssm.edu.
authors.forename: J C
authors.initials: JC
authors.lastname: Iatridis
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019149:Bioreactors; D002417:Cattle; D002648:Child; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D015203:Reproducibility of Results
keywords: Bioreactor loading system; Bovine; Human; Intervertebral disc; Organ culture
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