Large animal in vivo evaluation of a binary blend polymer scaffold for skeletal tissue-engineering strategies: translational issues

Smith, James O, Tayton, Edward R, Khan, Ferdous, Aarvold, Alexander, Cook, Richard, Goodship, Allen, Bradley, Mark and Oreffo, Richard (2015) Large animal in vivo evaluation of a binary blend polymer scaffold for skeletal tissue-engineering strategies: translational issues. Journal of Tissue Engineering and Regenerative Medicine, 11 (4), 1065-1076. (doi:10.1002/term.2007).

Abstract

Binary blend polymers offer the opportunity to combine different desirable properties into a single scaffold, to enhance function within the field of tissue engineering. Previous in vitro and murine in vivo analysis identified a polymer blend of poly(l‐lactic acid)–poly(ε‐caprolactone) (PLLA:PCL 20:80) to have characteristics desirable for bone regeneration. Polymer scaffolds in combination with marrow‐derived skeletal stem cells (SSCs) were implanted into mid‐shaft ovine 3.5 cm tibial defects, and indices of bone regeneration were compared to groups implanted with scaffolds alone and with empty defects after 12 weeks, including micro‐CT, mechanical testing and histological analysis. The critical nature of the defect was confirmed via all modalities. Both the scaffold and scaffold/SSC groups showed enhanced quantitative bone regeneration; however, this was only found to be significant in the scaffold/SSCs group (p = 0.04) and complete defect bridging was not achieved in any group. The mechanical strength was significantly less than that of contralateral control tibiae (p < 0.01) and would not be appropriate for full functional loading in a clinical setting. This study explored the hypothesis that cell therapy would enhance bone formation in a critical‐sized defect compared to scaffold alone, using an external fixation construct, to bridge the scale‐up gap between small animal studies and potential clinical translation. The model has proved a successful critical defect and analytical techniques have been found to be both valid and reproducible. Further work is required with both scaffold production techniques and cellular protocols in order to successfully scale‐up this stem cell/binary blend polymer scaffold.

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Contributors

Author: Richard Cook

Author: Richard Oreffo

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