Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model

J Lam; S Lu; E J Lee; J E Trachtenberg; V V Meretoja; R L Dahlin; J J J P van den Beucken; Y Tabata; M E Wong; J A Jansen; A G Mikos; F K Kasper

doi:10.1016/j.joca.2014.06.035

Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model

Osteoarthritis Cartilage. 2014 Sep;22(9):1291-300. doi: 10.1016/j.joca.2014.06.035. Epub 2014 Jul 4.

Authors

J Lam¹, S Lu¹, E J Lee¹, J E Trachtenberg¹, V V Meretoja¹, R L Dahlin¹, J J J P van den Beucken², Y Tabata³, M E Wong⁴, J A Jansen², A G Mikos⁵, F K Kasper⁶

Affiliations

¹ Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA.
² Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands.
³ Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
⁴ Department of Surgery, Division of Oral and Maxillofacial Surgery, The University of Texas School of Dentistry, Houston, TX, USA.
⁵ Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA. Electronic address: mikos@rice.edu.
⁶ Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA. Electronic address: kasper@rice.edu.

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.

Keywords: Chondrogenic; Hydrogel; Mesenchymal stem cell; Osteochondral repair; Osteogenic; Pre-differentiation.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Absorbable Implants
Animals
Cartilage, Articular / injuries*
Cartilage, Articular / physiology
Cell Differentiation
Cells, Cultured
Chondrogenesis / physiology*
Disease Models, Animal
Femur / injuries*
Femur / physiology
Hydrogels
Male
Mesenchymal Stem Cell Transplantation / methods*
Mesenchymal Stem Cells / cytology
Osteogenesis / physiology*
Rabbits
Time Factors

Substances

Hydrogels

Grants and funding

R01 AR048756/AR/NIAMS NIH HHS/United States