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Evaluation of skeletal tissue repair, Part 2: Enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model

Evaluation of skeletal tissue repair, Part 2: Enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model
Evaluation of skeletal tissue repair, Part 2: Enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model
There is an unmet need for improved, effective tissue engineering strategies to replace or repair bone damaged through disease or injury. Recent research has focused on developing biomaterial scaffolds capable of spatially and temporally releasing combinations of bioactive growth factors, rather than individual molecules, to recapitulate repair pathways present in vivo. We have developed an ex vivo embryonic chick femur critical size defect model and applied the model in the study of novel extracellular matrix (ECM) hydrogel scaffolds containing spatio-temporal combinatorial growth factor-releasing microparticles and skeletal stem cells for bone regeneration. Alginate/bovine bone ECM (bECM) hydrogels combined with poly(d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PLDLGA) microparticles releasing dual combinations of vascular endothelial growth factor (VEGF), chondrogenic transforming growth factor beta 3 (TGF-β3) and the bone morphogenetic protein BMP2, with human adult Stro-1+bone marrow stromal cells (HBMSCs), were placed into 2mm central segmental defects in embryonic day 11 chick femurs and organotypically cultured. Hydrogels loaded with VEGF combinations induced host cell migration and type I collagen deposition. Combinations of TGF-β3/BMP2, particularly with Stro-1+HBMSCs, induced significant formation of structured bone matrix, evidenced by increased Sirius red-stained matrix together with collagen expression demonstrating birefringent alignment within hydrogels. This study demonstrates the successful use of the chick femur organotypic culture system as a high-throughput test model for scaffold/cell/growth factor therapies in regenerative medicine. Temporal release of dual growth factors, combined with enriched Stro-1+HBMSCs, improved the formation of a highly structured bone matrix compared to single release modalities. These studies highlight the potential of a unique alginate/bECM hydrogel dual growth factor release platform for bone repair.
bone repair, ECM hydrogel scaffolds, ex vivo model, embryonic femur, dual growth factor delivery
1742-7061
4197-4205
Smith, E.L.
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Kanczler, J.M.
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Gothard, D.
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Roberts, C.A.
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Wells, J.A.
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White, L.J.
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Qutachi, O.
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Sawkins, M.J.
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Peto, H.
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Rashidi, H.
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Rojo, L.
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Stevens, M.M.
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El Haj, A.J.
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Rose, F.R.A.J.
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Shakesheff, K.M.
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Oreffo, R.O.C.
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Smith, E.L.
d302ca02-1a83-43cc-ad13-b6ffd8c6aad8
Kanczler, J.M.
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Gothard, D.
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Roberts, C.A.
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Wells, J.A.
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White, L.J.
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Qutachi, O.
730ae651-dd27-4456-a53d-a3d189cdc474
Sawkins, M.J.
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Peto, H.
cb20051b-0372-4755-bf3e-53083f2d19d7
Rashidi, H.
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Rojo, L.
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Stevens, M.M.
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El Haj, A.J.
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Rose, F.R.A.J.
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Shakesheff, K.M.
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Oreffo, R.O.C.
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Smith, E.L., Kanczler, J.M., Gothard, D., Roberts, C.A., Wells, J.A., White, L.J., Qutachi, O., Sawkins, M.J., Peto, H., Rashidi, H., Rojo, L., Stevens, M.M., El Haj, A.J., Rose, F.R.A.J., Shakesheff, K.M. and Oreffo, R.O.C. (2014) Evaluation of skeletal tissue repair, Part 2: Enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model. Acta Biomaterialia, 10 (10), 4197-4205. (doi:10.1016/j.actbio.2014.05.025). (PMID:24907660)

Record type: Article

Abstract

There is an unmet need for improved, effective tissue engineering strategies to replace or repair bone damaged through disease or injury. Recent research has focused on developing biomaterial scaffolds capable of spatially and temporally releasing combinations of bioactive growth factors, rather than individual molecules, to recapitulate repair pathways present in vivo. We have developed an ex vivo embryonic chick femur critical size defect model and applied the model in the study of novel extracellular matrix (ECM) hydrogel scaffolds containing spatio-temporal combinatorial growth factor-releasing microparticles and skeletal stem cells for bone regeneration. Alginate/bovine bone ECM (bECM) hydrogels combined with poly(d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PLDLGA) microparticles releasing dual combinations of vascular endothelial growth factor (VEGF), chondrogenic transforming growth factor beta 3 (TGF-β3) and the bone morphogenetic protein BMP2, with human adult Stro-1+bone marrow stromal cells (HBMSCs), were placed into 2mm central segmental defects in embryonic day 11 chick femurs and organotypically cultured. Hydrogels loaded with VEGF combinations induced host cell migration and type I collagen deposition. Combinations of TGF-β3/BMP2, particularly with Stro-1+HBMSCs, induced significant formation of structured bone matrix, evidenced by increased Sirius red-stained matrix together with collagen expression demonstrating birefringent alignment within hydrogels. This study demonstrates the successful use of the chick femur organotypic culture system as a high-throughput test model for scaffold/cell/growth factor therapies in regenerative medicine. Temporal release of dual growth factors, combined with enriched Stro-1+HBMSCs, improved the formation of a highly structured bone matrix compared to single release modalities. These studies highlight the potential of a unique alginate/bECM hydrogel dual growth factor release platform for bone repair.

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e-pub ahead of print date: 4 June 2014
Published date: October 2014
Keywords: bone repair, ECM hydrogel scaffolds, ex vivo model, embryonic femur, dual growth factor delivery
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 367168
URI: http://eprints.soton.ac.uk/id/eprint/367168
ISSN: 1742-7061
PURE UUID: 08a9913b-f6f6-4b62-9f1f-3bfa5643a6b3
ORCID for J.M. Kanczler: ORCID iD orcid.org/0000-0001-7249-0414
ORCID for J.A. Wells: ORCID iD orcid.org/0000-0001-8272-0236
ORCID for R.O.C. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

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Date deposited: 23 Jul 2014 17:54
Last modified: 12 Jul 2024 01:48

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Contributors

Author: E.L. Smith
Author: J.M. Kanczler ORCID iD
Author: D. Gothard
Author: C.A. Roberts
Author: J.A. Wells ORCID iD
Author: L.J. White
Author: O. Qutachi
Author: M.J. Sawkins
Author: H. Peto
Author: H. Rashidi
Author: L. Rojo
Author: M.M. Stevens
Author: A.J. El Haj
Author: F.R.A.J. Rose
Author: K.M. Shakesheff
Author: R.O.C. Oreffo ORCID iD

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