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Bone induction at physiological doses of BMP through localization by clay nanoparticle gels

Bone induction at physiological doses of BMP through localization by clay nanoparticle gels
Bone induction at physiological doses of BMP through localization by clay nanoparticle gels
Bone Morphogenic Protein 2 (BMP2) can induce ectopic bone. This ability, which first motivated the widespread application of BMP2 in fracture healing and spinal arthrodesis has, more recently, been indicated as one of several serious adverse effects associated with the supra-physiological doses of BMP2 relied upon for clinical efficacy. Key to harnessing BMPs and other agents safely and effectively will be the ability to localize activity at a target site at substantially reduced doses. Clay (Laponite) nanoparticles can self assemble into gels under physiological conditions and bind growth factors for enhanced and localized efficacy. Here we show the ability to localize and enhance the activity of BMP2 to achieve ectopic bone formation at doses within the sub-microgram per ml range of concentrations sufficient to induce differentiation of responsive cell populations in vitro and at approximately 3000 fold lower than those employed in clinical practice.
0142-9612
16-23
Gibbs, D.M.R.
4e8e4ea5-eaf5-4f93-8baf-88b524885893
Black, C.R.M.
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Hulsart-Billstrom, G.
1be9b158-ba9e-48c7-bc68-78636c83c37c
Shi, P.
449619dc-0500-4fd7-bbbf-c2299e859519
Scarpa, E.
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Oreffo, R.O.C.
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Dawson, J.I.
b220fe76-498d-47be-9995-92da6c289cf3
Gibbs, D.M.R.
4e8e4ea5-eaf5-4f93-8baf-88b524885893
Black, C.R.M.
7f616e37-4d80-4f60-ac8d-ba96e583db72
Hulsart-Billstrom, G.
1be9b158-ba9e-48c7-bc68-78636c83c37c
Shi, P.
449619dc-0500-4fd7-bbbf-c2299e859519
Scarpa, E.
4957e445-a1d6-4ca9-9532-ccefada666bf
Oreffo, R.O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Dawson, J.I.
b220fe76-498d-47be-9995-92da6c289cf3

Gibbs, D.M.R., Black, C.R.M., Hulsart-Billstrom, G., Shi, P., Scarpa, E., Oreffo, R.O.C. and Dawson, J.I. (2016) Bone induction at physiological doses of BMP through localization by clay nanoparticle gels. Biomaterials, 99, 16-23. (doi:10.1016/j.biomaterials.2016.05.010). (PMID:27209259)

Record type: Article

Abstract

Bone Morphogenic Protein 2 (BMP2) can induce ectopic bone. This ability, which first motivated the widespread application of BMP2 in fracture healing and spinal arthrodesis has, more recently, been indicated as one of several serious adverse effects associated with the supra-physiological doses of BMP2 relied upon for clinical efficacy. Key to harnessing BMPs and other agents safely and effectively will be the ability to localize activity at a target site at substantially reduced doses. Clay (Laponite) nanoparticles can self assemble into gels under physiological conditions and bind growth factors for enhanced and localized efficacy. Here we show the ability to localize and enhance the activity of BMP2 to achieve ectopic bone formation at doses within the sub-microgram per ml range of concentrations sufficient to induce differentiation of responsive cell populations in vitro and at approximately 3000 fold lower than those employed in clinical practice.

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Accepted/In Press date: 4 May 2016
e-pub ahead of print date: 10 May 2016
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 395170
URI: http://eprints.soton.ac.uk/id/eprint/395170
ISSN: 0142-9612
PURE UUID: d02921fb-a67f-414a-9659-918d05d92790
ORCID for R.O.C. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726
ORCID for J.I. Dawson: ORCID iD orcid.org/0000-0002-6712-0598

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Date deposited: 27 May 2016 08:11
Last modified: 07 Oct 2020 06:02

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Contributors

Author: D.M.R. Gibbs
Author: C.R.M. Black
Author: G. Hulsart-Billstrom
Author: P. Shi
Author: E. Scarpa
Author: R.O.C. Oreffo ORCID iD
Author: J.I. Dawson ORCID iD

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