title: Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model.
abstract: OBJECTIVE
  To investigate the ability of cell-laden bilayered hydrogels encapsulating chondrogenically and osteogenically (OS) pre-differentiated mesenchymal stem cells (MSCs) to effect osteochondral defect repair in a rabbit model. By varying the period of chondrogenic pre-differentiation from 7 (CG7) to 14 days (CG14), the effect of chondrogenic differentiation stage on osteochondral tissue repair was also investigated.
  
  
  METHODS
  Rabbit MSCs were subjected to either chondrogenic or osteogenic pre-differentiation, encapsulated within respective chondral/subchondral layers of a bilayered hydrogel construct, and then implanted into femoral condyle osteochondral defects. Rabbits were randomized into one of four groups (MSC/MSC, MSC/OS, CG7/OS, and CG14/OS; chondral/subchondral) and received two similar constructs bilaterally. Defects were evaluated after 12 weeks.
  
  
  RESULTS
  All groups exhibited similar overall neo-tissue filling. The delivery of OS cells when compared to undifferentiated MSCs in the subchondral construct layer resulted in improvements in neo-cartilage thickness and regularity. However, the addition of CG cells in the chondral layer, with OS cells in the subchondral layer, did not augment tissue repair as influenced by the latter when compared to the control. Instead, CG7/OS implants resulted in more irregular neo-tissue surfaces when compared to MSC/OS implants. Notably, the delivery of CG7 cells, when compared to CG14 cells, with OS cells stimulated morphologically superior cartilage repair. However, neither osteogenic nor chondrogenic pre-differentiation affected detectable changes in subchondral tissue repair.
  
  
  CONCLUSIONS
  Cartilage regeneration in osteochondral defects can be enhanced by MSCs that are chondrogenically and osteogenically pre-differentiated prior to implantation. Longer chondrogenic pre-differentiation periods, however, lead to diminished cartilage repair.
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lam
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Trachtenberg
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA.
authors.forename: V V
authors.initials: VV
authors.lastname: Meretoja
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Dahlin
authors.affiliation: Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands.
authors.forename: J J J P
authors.initials: JJ
authors.lastname: van den Beucken
authors.affiliation: Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Department of Surgery, Division of Oral and Maxillofacial Surgery, The University of Texas School of Dentistry, Houston, TX, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Wong
authors.affiliation: Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Jansen
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA. Electronic address: mikos@rice.edu.
authors.forename: A G
authors.initials: AG
authors.lastname: Mikos
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA. Electronic address: kasper@rice.edu.
authors.forename: F K
authors.initials: FK
authors.lastname: Kasper
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002358:Cartilage, Articular / Q000293:injuries* / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology*; D004195:Disease Models, Animal; D005269:Femur / Q000293:injuries* / Q000502:physiology; D020100:Hydrogels; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010012:Osteogenesis / Q000502:physiology*; D011817:Rabbits; D013997:Time Factors
chemical_list: D020100:Hydrogels
keywords: Chondrogenic; Hydrogel; Mesenchymal stem cell; Osteochondral repair; Osteogenic; Pre-differentiation