A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs

Adam B. Nover, Brian K. Jones, William T. Yu, Daniel S. Donovan, Jeremy D. Podolnick, James L. Cook, Gerard A. Ateshian, Clark T. Hung

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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[U+05F3]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.

Original languageEnglish
Pages (from-to)668-677
Number of pages10
JournalJournal of Biomechanics
Issue number5
StatePublished - 21 Mar 2016
Externally publishedYes


  • Articular cartilage
  • Nutrient limitations
  • Puzzle
  • Scaling up
  • Tissue engineering


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