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Osteochondral Interface Tissue Engineering Using Macroscopic Gradients of Bioactive Signals

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Bioengineering Program, University of Kansas, Lawrence, KS, 66045, USA

    Nathan H. Dormer

  2. Department of Bioengineering, Rice University, Houston, TX, 77005, USA

    Milind Singh

  3. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA

    Limin Wang

  4. Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, 66045, USA

    Cory J. Berkland

  5. Department of Chemical and Petroleum Engineering, University of Kansas, 1530 W 15th Street, 4132 Learned Hall, Lawrence, KS, 66045, USA

    Cory J. Berkland & Michael S. Detamore

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  1. Nathan H. Dormer
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Correspondence to Michael S. Detamore.

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Dormer, N.H., Singh, M., Wang, L. et al. Osteochondral Interface Tissue Engineering Using Macroscopic Gradients of Bioactive Signals. Ann Biomed Eng 38, 2167–2182 (2010). https://doi.org/10.1007/s10439-010-0028-0

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