title: Challenges in engineering osteochondral tissue grafts with hierarchical structures.
abstract: BACKGROUND
  A major hurdle in treating osteochondral (OC) defects is the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair.
  
  
  METHODS
  This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research.
  
  
  CONCLUSIONS
  A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens and harnessing of inflammatory responses of the host will likely drive the further progress.
authors.affiliation: a 1 Belgrade Metropolitan University, Center for Bioengineering - BioIRC , Prvoslava Stojanovica 6, 34000 Kragujevac, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Gadjanski
authors.affiliation: b 2 Columbia University, Laboratory for Stem Cells and Tissue Engineering , 622 west 168th Street, VC12-234, New York, NY, USA +1 212 305 2304 ; +1 212 305 4692 ; gv2131@columbia.edu.
authors.forename: Gordana
authors.initials: G
authors.lastname: Vunjak-Novakovic
mesh_terms: D032701:Biomimetics; D001847:Bone Diseases / Q000628:therapy; D001854:Bone Marrow Cells / Q000166:cytology; D002358:Cartilage, Articular / Q000502:physiology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D012038:Regeneration; D044968:Regenerative Medicine; D023822:Tissue Engineering; D054457:Tissue Scaffolds
keywords: anatomical shape; biomimetics; osteochondral grafts; tissue engineering