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Microparticles for controlled GDF6 delivery to direct ASC‐based nucleus pulposus regeneration

Hodgkinson, Tom; Stening, Jasmine Z.; White, Lisa J.; Shakesheff, Kevin M.; Hoyland, Judith A.; Richardson, Stephen M.

Authors

Tom Hodgkinson

Jasmine Z. Stening

Kevin M. Shakesheff

Judith A. Hoyland

Stephen M. Richardson



Contributors

Kevin Shakesheff

Abstract

Currently, there is no effective long-term treatment for intervertebral disc degeneration (IVDD), making it an attractive candidate for regenerative therapies. Hydrogel delivery of adipose stem cells (ASCs) in combination with controlled release of bioactive molecules is a promising approach to halt IVDD and promote regeneration. Growth differentiation factor (GDF)6 can induce ASC differentiation into anabolic nucleus pulposus (NP) cells and hence holds promise for IVD regeneration. Here, we optimised design of novel PLGA-PEG-PLGA microparticles to control GDF6 delivery and investigated effect of released GDF6 on human ASCs differentiation to NP cells. Recombinant human (rh)GDF6 was loaded into microparticles and total protein and rhGDF6 release assessed. The effect of microparticle loading density on distribution and gel formation was investigated through scanning electron microscopy. ASC differentiation to NP cells was examined after 14 days in hydrogel culture by qPCR, histological and immunohistochemical staining in normoxic and IVD-like hypoxic conditions. RhGDF6-microparticles were distributed throughout gels without disrupting gelation and controlled rhGDF6 release over 14 days. Released GDF6 significantly induced NP differentiation of ASCs, with expression comparable to or exceeding media supplemented rhGDF6. Microparticle-delivered rhGDF6 also up-regulated sGAG and aggrecan secretion in comparison to controls. In hypoxia, microparticle-delivered rhGDF6 continued to effectively induce NP gene expression and aggrecan production. This study demonstrates the effective encapsulation and controlled delivery of rhGDF6, which maintained its activity and induced ASC differentiation to NP cells and synthesis of a NP-like matrix suggesting suitability of microparticles for controlled growth factor release in regenerative strategies for treatment of IVDD.  

Citation

Hodgkinson, T., Stening, J. Z., White, L. J., Shakesheff, K. M., Hoyland, J. A., & Richardson, S. M. (2019). Microparticles for controlled GDF6 delivery to direct ASC‐based nucleus pulposus regeneration. Journal of Tissue Engineering and Regenerative Medicine, 13(8), 1406-1417. https://doi.org/10.1002/term.2882

Journal Article Type Article
Acceptance Date Apr 29, 2019
Online Publication Date May 8, 2019
Publication Date May 8, 2019
Deposit Date May 20, 2019
Publicly Available Date Aug 13, 2019
Journal Journal of Tissue Engineering and Regenerative Medicine
Print ISSN 1932-6254
Electronic ISSN 1932-7005
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 13
Issue 8
Pages 1406-1417
DOI https://doi.org/10.1002/term.2882
Keywords Medicine (miscellaneous); Biomaterials; Biomedical Engineering
Public URL https://nottingham-repository.worktribe.com/output/2074001
Publisher URL https://onlinelibrary.wiley.com/doi/abs/10.1002/term.2882

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