Annals of Biomedical Engineering

, Volume 38, Issue 6, pp 2167–2182 | Cite as

Osteochondral Interface Tissue Engineering Using Macroscopic Gradients of Bioactive Signals

  • Nathan H. Dormer
  • Milind Singh
  • Limin Wang
  • Cory J. Berkland
  • Michael S. DetamoreEmail author


Continuous gradients exist at osteochondral interfaces, which may be engineered by applying spatially patterned gradients of biological cues. In the present study, a protein-loaded microsphere-based scaffold fabrication strategy was applied to achieve spatially and temporally controlled delivery of bioactive signals in three-dimensional (3D) tissue engineering scaffolds. Bone morphogenetic protein-2 and transforming growth factor-β1-loaded poly(d,l-lactic-co-glycolic acid) microspheres were utilized with a gradient scaffold fabrication technology to produce microsphere-based scaffolds containing opposing gradients of these signals. Constructs were then seeded with human bone marrow stromal cells (hBMSCs) or human umbilical cord mesenchymal stromal cells (hUCMSCs), and osteochondral tissue regeneration was assessed in gradient scaffolds and compared to multiple control groups. Following a 6-week cell culture, the gradient scaffolds produced regionalized extracellular matrix, and outperformed the blank control scaffolds in cell number, glycosaminoglycan production, collagen content, alkaline phosphatase activity, and in some instances, gene expression of major osteogenic and chondrogenic markers. These results suggest that engineered signal gradients may be beneficial for osteochondral tissue engineering.


Osteochondral Interface Gradient Microsphere Umbilical cord stem cells PLGA BMP-2 TGF-β1 



The authors would like to express their gratitude to the Arthritis Foundation, the National Institutes of Health (NIH/NIDCR 1 R21 DE017673-01) for their support, to NIGMS/NIH Pharmaceutical Aspects of Biotechnology Training grant (T32-GM008359) for supporting N. H. Dormer, and to Dr. Xinkun Wang of the K.U. Genomics Facility for his guidance in RT–PCR.

Supplementary material

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Supplementary material 1 (DOCX 159 kb)
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Supplementary material 2 (DOCX 63 kb)
10439_2010_28_MOESM3_ESM.docx (261 kb)
Supplementary material 3 (DOCX 329 kb)
10439_2010_28_MOESM4_ESM.docx (224 kb)
Supplementary material 4 (DOCX 223 kb)


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Copyright information

© Biomedical Engineering Society 2010

Authors and Affiliations

  • Nathan H. Dormer
    • 1
  • Milind Singh
    • 2
  • Limin Wang
    • 3
  • Cory J. Berkland
    • 4
    • 5
  • Michael S. Detamore
    • 5
    Email author
  1. 1.Bioengineering ProgramUniversity of KansasLawrenceUSA
  2. 2.Department of BioengineeringRice UniversityHoustonUSA
  3. 3.Department of Biomedical EngineeringUniversity of MichiganAnn ArborUSA
  4. 4.Department of Pharmaceutical ChemistryUniversity of KansasLawrenceUSA
  5. 5.Department of Chemical and Petroleum EngineeringUniversity of KansasLawrenceUSA

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