title: Three-dimensional osteogenic and chondrogenic systems to model osteochondral physiology and degenerative joint diseases.
abstract: Tissue engineered constructs have the potential to function as in vitro pre-clinical models of normal tissue function and disease pathogenesis for drug screening and toxicity assessment. Effective high throughput assays demand minimal systems with clearly defined performance parameters. These systems must accurately model the structure and function of the human organs and their physiological response to different stimuli. Musculoskeletal tissues present unique challenges in this respect, as they are load-bearing, matrix-rich tissues whose functionality is intimately connected to the extracellular matrix and its organization. Of particular clinical importance is the osteochondral junction, the target tissue affected in degenerative joint diseases, such as osteoarthritis (OA), which consists of hyaline articular cartilage in close interaction with subchondral bone. In this review, we present an overview of currently available in vitro three-dimensional systems for bone and cartilage tissue engineering that mimic native physiology, and the utility and limitations of these systems. Specifically, we address the need to combine bone, cartilage and other tissues to form an interactive microphysiological system (MPS) to fully capture the biological complexity and mechanical functions of the osteochondral junction of the articular joint. The potential applications of three-dimensional MPSs for musculoskeletal biology and medicine are highlighted.
authors.affiliation: Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, 15219 USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Alexander
authors.affiliation: Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, 15219 USA Ri.MED Foundation, Palermo, I-90133 Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gottardi
authors.affiliation: Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, 15219 USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Lin
authors.affiliation: Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, 15219 USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lozito
authors.affiliation: Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, 15219 USA Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA 15261, USA Department of Mechanical Engineering and Materials Science, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA 15261, USA rst13@pitt.edu.
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
mesh_terms: D000818:Animals; D020219:Chondrogenesis; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D010003:Osteoarthritis / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D010012:Osteogenesis; D046509:Tissue Culture Techniques / Q000295:instrumentation* / Q000379:methods*
keywords: Tissue engineering; biomaterial scaffold; bone; cartilage; drug screening; osteoarthritis