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Pore Geometry Regulates Early Stage Human Bone Marrow Cell Tissue Formation and Organisation

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Abstract

Porous architecture has a dramatic effect on tissue formation in porous biomaterials used in regenerative medicine. However, the wide variety of 3D structures used indicates there is a clear need for the optimal design of pore architecture to maximize tissue formation and ingrowth. Thus, the aim of this study was to characterize initial tissue growth solely as a function of pore geometry. We used an in vitro system with well-defined open pore slots of varying width, providing a 3D environment for neo-tissue formation while minimizing nutrient limitations. Results demonstrated that initial tissue formation was strongly influenced by pore geometry. Both velocity of tissue invasion and area of tissue formed increased as pores became narrower. This is associated with distinct patterns of actin organisation and alignment depending on pore width, indicating the role of active cell generated forces. A mathematical model based on curvature driven growth successfully predicted both shape of invasion front and constant rate of growth, which increased for narrower pores as seen in experiments. Our results provide further evidence for a front based, curvature driven growth mechanism depending on pore geometry and tissue organisation, which could provide important clues for 3D scaffold design.

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Acknowledgments

We would like to thank Dr R. Tare and the Bone and Joint Research Group in Southampton for their assistance and for providing the cell sample. Dr C. Catt was supported by Symbiosis project funding, EPSRC EP/F032994/1.

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Authors and Affiliations

  1. Bioengineering Science Research Group, Faculty of Engineering and the Environment, University of Southampton, Highfield, Southampton, SO17 1BJ, UK

    J. Knychala, O. L. Katsamenis & B. G. Sengers

  2. Department of Materials Science, University of Patras, 26504, Rio, Patras, Greece

    N. Bouropoulos & O. L. Katsamenis

  3. Foundation for Research and Technology, Hellas-Institute of Chemical Engineering and High Temperature Chemical Processes—FORTH/ICE-HT, P.O. Box 1414, 26504, Patras, Greece

    N. Bouropoulos

  4. School of Mathematics, University of Southampton, Highfield, Southampton, SO17 1BJ, UK

    C. J. Catt & C. P. Please

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  1. J. Knychala
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  2. N. Bouropoulos
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  3. C. J. Catt
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  4. O. L. Katsamenis
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  5. C. P. Please
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Correspondence to J. Knychala.

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Associate Editor Smadar Cohen oversaw the review of this article.

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10439_2013_748_MOESM1_ESM.tif

Fig. S1 (a) Example of a 3D reconstruction of the actin network in a 400 μm pore (70 μm z-stack, pore walls were indicated manually for illustrative purposes only). (b) Perpendicular cross section along the y–z plane showing the thin cell layer at the immediate front. (c) Longitudinal cross section along (x–z) plane showing tissue thickening away from the front of migration (TIFF 1580 kb)

10439_2013_748_MOESM2_ESM.avi

Fig. S2 & S3 Time lapse video recorded for 10 h, pictures taken every 20 min for 200 μm (S2) and 500 μm (S3) (AVI 22,715 kb)

Supplementary material 3 (AVI 16,376 kb)

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Knychala, J., Bouropoulos, N., Catt, C.J. et al. Pore Geometry Regulates Early Stage Human Bone Marrow Cell Tissue Formation and Organisation. Ann Biomed Eng 41, 917–930 (2013). https://doi.org/10.1007/s10439-013-0748-z

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