title: A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs.
abstract: Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young׳s modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects.
authors.affiliation: Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, Mail Code: 8904, New York, NY 10027, USA. Electronic address: abn2106@columbia.edu.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Nover
authors.affiliation: Department of Mechanical Engineering, Columbia University, 242 S. W. Mudd, 500 West 120th Street, Mail Code: 4703, New York, NY 10027, USA. Electronic address: bkj2106@columbia.edu.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Jones
authors.affiliation: Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, Mail Code: 8904, New York, NY 10027, USA. Electronic address: wty2102@columbia.edu.
authors.forename: William T
authors.initials: WT
authors.lastname: Yu
authors.affiliation: Department of Orthopedic Surgery, Mount Sinai West, 1000 Tenth Avenue, New York, NY 10019, USA; Department of Orthopedic Surgery, Mount Sinai St. Luke׳s, 1111 Amsterdam Avenue, New York, NY 10025, USA. Electronic address: dandonovan@chpnet.org.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Donovan
authors.affiliation: Department of Orthopedic Surgery, Mount Sinai West, 1000 Tenth Avenue, New York, NY 10019, USA; Department of Orthopedic Surgery, Mount Sinai St. Luke׳s, 1111 Amsterdam Avenue, New York, NY 10025, USA. Electronic address: jpodolnick@chpnet.org.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Podolnick
authors.affiliation: Department of Orthopaedic Surgery, University of Missouri, 1100 Virginia Avenue, DC953.000, Columbia, MO 65212, USA. Electronic address: CookJL@missouri.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Cook
authors.affiliation: Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, Mail Code: 8904, New York, NY 10027, USA; Department of Mechanical Engineering, Columbia University, 242 S. W. Mudd, 500 West 120th Street, Mail Code: 4703, New York, NY 10027, USA. Electronic address: ateshian@columbia.edu.
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Ateshian
authors.affiliation: Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, Mail Code: 8904, New York, NY 10027, USA. Electronic address: cth6@columbia.edu.
authors.forename: Clark T
authors.initials: CT
authors.lastname: Hung
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology*; D018929:Cell Culture Techniques; D019902:Chondrocytes / Q000166:cytology; D055119:Elastic Modulus; D055595:Mechanical Phenomena; D051379:Mice; D023822:Tissue Engineering / Q000379:methods*
keywords: Articular cartilage; Nutrient limitations; Puzzle; Scaling up; Tissue engineering