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

Large animal in vivo evaluation of a binary blend polymer scaffold for skeletal tissue-engineering strategies: translational issues
Large animal in vivo evaluation of a binary blend polymer scaffold for skeletal tissue-engineering strategies: translational issues
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.
1932-6254
1065-1076
Smith, James O
32dd9c6a-acc3-4f8a-bfb8-f74d9890b0be
Tayton, Edward R
fcd62901-6668-4de8-8bf5-0b2f18bbf659
Khan, Ferdous
e25017a8-e13b-493c-a211-65093dd5c3fa
Aarvold, Alexander
11dc317f-47fd-4b2c-b0a6-78688c679b5a
Cook, Richard
06f8322d-81be-4f82-9326-19e55541c78f
Goodship, Allen
b727629e-3d3d-4c30-a6b8-ff4e08d3f775
Bradley, Mark
562b9add-34c4-4620-bfa1-c7c83a0f0900
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Smith, James O
32dd9c6a-acc3-4f8a-bfb8-f74d9890b0be
Tayton, Edward R
fcd62901-6668-4de8-8bf5-0b2f18bbf659
Khan, Ferdous
e25017a8-e13b-493c-a211-65093dd5c3fa
Aarvold, Alexander
11dc317f-47fd-4b2c-b0a6-78688c679b5a
Cook, Richard
06f8322d-81be-4f82-9326-19e55541c78f
Goodship, Allen
b727629e-3d3d-4c30-a6b8-ff4e08d3f775
Bradley, Mark
562b9add-34c4-4620-bfa1-c7c83a0f0900
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778

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).

Record type: Article

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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Published date: 18 February 2015

Identifiers

Local EPrints ID: 433422
URI: http://eprints.soton.ac.uk/id/eprint/433422
ISSN: 1932-6254
PURE UUID: 5947e5d9-b6d0-4b4e-88ba-a96ae3ad4286
ORCID for Richard Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

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Date deposited: 21 Aug 2019 16:30
Last modified: 17 Dec 2019 01:53

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Contributors

Author: James O Smith
Author: Edward R Tayton
Author: Ferdous Khan
Author: Alexander Aarvold
Author: Richard Cook
Author: Allen Goodship
Author: Mark Bradley
Author: Richard Oreffo ORCID iD

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