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Evaluation of skeletal tissue repair, Part 1: Assessment of novel growth-factor-releasing hydrogels in an ex vivo chick femur defect model

Evaluation of skeletal tissue repair, Part 1: Assessment of novel growth-factor-releasing hydrogels in an ex vivo chick femur defect model
Evaluation of skeletal tissue repair, Part 1: Assessment of novel growth-factor-releasing hydrogels in an ex vivo chick femur defect model
Current clinical treatments for skeletal conditions resulting in large-scale bone loss include autograft or allograft, both of which have limited effectiveness. In seeking to address bone regeneration, several tissue engineering strategies have come to the fore, including the development of growth factor releasing technologies and appropriate animal models to evaluate repair. Ex vivo models represent a promising alternative to simple in vitro systems or complex, ethically challenging in vivo models. We have developed an ex vivo culture system of whole embryonic chick femora, adapted in this study as a critical size defect model to investigate the effects of novel bone extracellular matrix (bECM) hydrogel scaffolds containing spatio-temporal growth factor-releasing microparticles and skeletal stem cells on bone regeneration, to develop a viable alternative treatment for skeletal degeneration. Alginate/bECM hydrogels combined with poly (d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PDLLGA) microparticles releasing VEGF, TGF-β3 or BMP-2 were placed, with human adult Stro-1+ bone marrow stromal cells, into 2mm central segmental defects in embryonic chick femurs. Alginate/bECM hydrogels loaded with HSA/VEGF or HSA/TGF-β3 demonstrated a cartilage-like phenotype, with minimal collagen I deposition, comparable to HSA-only control hydrogels. The addition of BMP-2 releasing microparticles resulted in enhanced structured bone matrix formation, evidenced by increased Sirius red-stained matrix and collagen expression within hydrogels. This study demonstrates delivery of bioactive growth factors from a novel alginate/bECM hydrogel to augment skeletal tissue formation and the use of an organotypic chick femur defect culture system as a high-throughput test model for scaffold/cell/growth factor therapies for regenerative medicine.
bone repair, ECM hydrogel scaffolds, ex vivo model, embryonic femur, bioactive growth factor delivery
1742-7061
4186-4196
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.
eb8db9ff-a038-475f-9030-48eef2b0559c
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.
e50b878e-718a-4427-8f36-0b048d976c63
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., 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 1: Assessment of novel growth-factor-releasing hydrogels in an ex vivo chick femur defect model. Acta Biomaterialia, 10 (10), 4186-4196. (doi:10.1016/j.actbio.2014.06.011). (PMID:24937137)

Record type: Article

Abstract

Current clinical treatments for skeletal conditions resulting in large-scale bone loss include autograft or allograft, both of which have limited effectiveness. In seeking to address bone regeneration, several tissue engineering strategies have come to the fore, including the development of growth factor releasing technologies and appropriate animal models to evaluate repair. Ex vivo models represent a promising alternative to simple in vitro systems or complex, ethically challenging in vivo models. We have developed an ex vivo culture system of whole embryonic chick femora, adapted in this study as a critical size defect model to investigate the effects of novel bone extracellular matrix (bECM) hydrogel scaffolds containing spatio-temporal growth factor-releasing microparticles and skeletal stem cells on bone regeneration, to develop a viable alternative treatment for skeletal degeneration. Alginate/bECM hydrogels combined with poly (d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PDLLGA) microparticles releasing VEGF, TGF-β3 or BMP-2 were placed, with human adult Stro-1+ bone marrow stromal cells, into 2mm central segmental defects in embryonic chick femurs. Alginate/bECM hydrogels loaded with HSA/VEGF or HSA/TGF-β3 demonstrated a cartilage-like phenotype, with minimal collagen I deposition, comparable to HSA-only control hydrogels. The addition of BMP-2 releasing microparticles resulted in enhanced structured bone matrix formation, evidenced by increased Sirius red-stained matrix and collagen expression within hydrogels. This study demonstrates delivery of bioactive growth factors from a novel alginate/bECM hydrogel to augment skeletal tissue formation and the use of an organotypic chick femur defect culture system as a high-throughput test model for scaffold/cell/growth factor therapies for regenerative medicine.

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e-pub ahead of print date: 14 June 2014
Published date: October 2014
Keywords: bone repair, ECM hydrogel scaffolds, ex vivo model, embryonic femur, bioactive growth factor delivery
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 367167
URI: http://eprints.soton.ac.uk/id/eprint/367167
ISSN: 1742-7061
PURE UUID: 73148d8b-9347-49ea-ba7d-10623a6d6297
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 17:31
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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