The Combined Effect of Substrate Stiffness and Surface Topography on Chondrogenic Differentiation of Mesenchymal Stem Cells.
Stem cell differentiation is guided by contact with the physical microenvironment, influence by both topography and mechanical properties of the matrix. In this study, the combined effect of substratum nano-topography and mechanical stiffness in directing mesenchymal stem cell (MSC) chondrogenesis was investigated. Three polyesters of varying stiffness were thermally imprinted to create nano-grating or pillar patterns of the same dimension. The surface of the nano-patterned substrate was coated with chondroitin sulfate (CS) to provide an even surface chemistry, with cell-adhesive and chondro-inductive properties, across all polymeric substrates. The surface characteristic, mechanical modulus, and degradation of the CS-coated patterned polymeric substrates were analyzed. The cell morphology adopted on the nano-topographic surfaces were accounted by F-actin distribution, and correlated to the cell proliferation and chondrogenic differentiation outcomes. Results show that substratum stiffness and topographical cues affected MSC morphology and aggregation, and influenced the phenotypic development at the earlier stage of chondrogenic differentiation. Hyaline-like cartilage with middle/deep zone cartilage characteristics was generated on softer pillar surface, while on stiffer nano-pillar material MSCs showed potential to generate constituents of hyaline/fibro/hypertrophic cartilage. Fibro/superficial zone-like cartilage could be derived from nano-grating of softer stiffness, while stiffer nano-grating resulted in insignificant chondrogenesis. This study demonstrates the possibility of refining the phenotype of cartilage generated from MSCs by manipulating surface topography and material stiffness.
1 Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore , Singapore .|2 Tissue Engineering Program, Life Sciences Institute, National University of Singapore , Singapore .
Yingnan
Y
Wu
1 Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore , Singapore .|2 Tissue Engineering Program, Life Sciences Institute, National University of Singapore , Singapore .
Zheng
Z
Yang
3 Institute of Materials Research and Engineering , A*STAR (Agency for Science, Technology and Research), Singapore .
Jaslyn Bee Khuan
JB
Law
3 Institute of Materials Research and Engineering , A*STAR (Agency for Science, Technology and Research), Singapore .
Ai Yu
AY
He
4 Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya , Pantai Valley, Kuala Lumpur, Malaysia .
Azlina A
AA
Abbas
1 Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore , Singapore .
Vinitha
V
Denslin
4 Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence for Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya , Pantai Valley, Kuala Lumpur, Malaysia .
Tunku
T
Kamarul
1 Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore , Singapore .|2 Tissue Engineering Program, Life Sciences Institute, National University of Singapore , Singapore .
James H P
JH
Hui
1 Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore , Singapore .|2 Tissue Engineering Program, Life Sciences Institute, National University of Singapore , Singapore .|5 Mechanobiology Institute, National University of Singapore , Singapore .
Eng Hin
EH
Lee
D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis; D002809:Chondroitin Sulfates / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D019245:Compressive Strength; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D013499:Surface Properties
D020099:Coated Materials, Biocompatible; D002809:Chondroitin Sulfates
cartilage; chondrogenesis; mesenchymal stem cells; nano-topography; stiffness