Local injection of a hexametaphosphate formulation reduces heterotopic ossification in vivo

Research output: Contribution to journalArticlepeer-review

Standard

Local injection of a hexametaphosphate formulation reduces heterotopic ossification in vivo. / Robinson, Thomas; Eisenstein, Neil; Cox, Sophie; Moakes, Richard; Thompson, Adam M; Ahmed, Zubair; Hughes, Erik; Hill, Lisa J; Stapley, Sarah; Grover, Liam.

In: Materials today. Bio, Vol. 7, 100059, 06.2020.

Research output: Contribution to journalArticlepeer-review

Harvard

APA

Vancouver

Author

Bibtex

@article{99c7111f0c0f427c8ee8e0808858c7e9,
title = "Local injection of a hexametaphosphate formulation reduces heterotopic ossification in vivo",
abstract = "Heterotopic ossification (HO), the pathological formation of ectopic bone, is a debilitating condition which can cause chronic pain, limit joint movement, and prevent prosthetic limb fitting. The prevalence of this condition has risen in the military population, due to increased survivorship following blast injuries. Current prophylaxes, which aim to target the complex upstream biological pathways, are inconsistently effective ​and have a range of side-effects that make them unsuitable for combat-injured personnel. As such, many patients must undergo further surgery to remove the formed ectopic bone. In this study, a non-toxic, U.S. Food and Drug Administration (FDA) -approved calcium chelator, hexametaphosphate (HMP), is explored as a novel treatment paradigm for this condition, which targets the chemical, rather that biological, ​bone formation pathways. This approach allows not only prevention of pathological bone formation ​but also uniquely facilitates reversal, which current drugs cannot achieve. Targeted, minimally invasive delivery is achieved by loading HMP into an injectable colloidal alginate. These formulations significantly reduce ​the length of the ectopic bone formed in a rodent model of HO, with no effect on the adjacent skeletal bone. This study demonstrates the potential of localized dissolution as a new treatment ​and an alternative to surgery ​for pathological ossification and calcification conditions.",
keywords = "Ectopic bone, Alginate, Biomaterial, Polyphosphate, Targeted delivery",
author = "Thomas Robinson and Neil Eisenstein and Sophie Cox and Richard Moakes and Thompson, {Adam M} and Zubair Ahmed and Erik Hughes and Hill, {Lisa J} and Sarah Stapley and Liam Grover",
year = "2020",
month = jun,
doi = "10.1016/j.mtbio.2020.100059",
language = "English",
volume = "7",
journal = "Materials today. Bio",
issn = "2590-0064",

}

RIS

TY - JOUR

T1 - Local injection of a hexametaphosphate formulation reduces heterotopic ossification in vivo

AU - Robinson, Thomas

AU - Eisenstein, Neil

AU - Cox, Sophie

AU - Moakes, Richard

AU - Thompson, Adam M

AU - Ahmed, Zubair

AU - Hughes, Erik

AU - Hill, Lisa J

AU - Stapley, Sarah

AU - Grover, Liam

PY - 2020/6

Y1 - 2020/6

N2 - Heterotopic ossification (HO), the pathological formation of ectopic bone, is a debilitating condition which can cause chronic pain, limit joint movement, and prevent prosthetic limb fitting. The prevalence of this condition has risen in the military population, due to increased survivorship following blast injuries. Current prophylaxes, which aim to target the complex upstream biological pathways, are inconsistently effective ​and have a range of side-effects that make them unsuitable for combat-injured personnel. As such, many patients must undergo further surgery to remove the formed ectopic bone. In this study, a non-toxic, U.S. Food and Drug Administration (FDA) -approved calcium chelator, hexametaphosphate (HMP), is explored as a novel treatment paradigm for this condition, which targets the chemical, rather that biological, ​bone formation pathways. This approach allows not only prevention of pathological bone formation ​but also uniquely facilitates reversal, which current drugs cannot achieve. Targeted, minimally invasive delivery is achieved by loading HMP into an injectable colloidal alginate. These formulations significantly reduce ​the length of the ectopic bone formed in a rodent model of HO, with no effect on the adjacent skeletal bone. This study demonstrates the potential of localized dissolution as a new treatment ​and an alternative to surgery ​for pathological ossification and calcification conditions.

AB - Heterotopic ossification (HO), the pathological formation of ectopic bone, is a debilitating condition which can cause chronic pain, limit joint movement, and prevent prosthetic limb fitting. The prevalence of this condition has risen in the military population, due to increased survivorship following blast injuries. Current prophylaxes, which aim to target the complex upstream biological pathways, are inconsistently effective ​and have a range of side-effects that make them unsuitable for combat-injured personnel. As such, many patients must undergo further surgery to remove the formed ectopic bone. In this study, a non-toxic, U.S. Food and Drug Administration (FDA) -approved calcium chelator, hexametaphosphate (HMP), is explored as a novel treatment paradigm for this condition, which targets the chemical, rather that biological, ​bone formation pathways. This approach allows not only prevention of pathological bone formation ​but also uniquely facilitates reversal, which current drugs cannot achieve. Targeted, minimally invasive delivery is achieved by loading HMP into an injectable colloidal alginate. These formulations significantly reduce ​the length of the ectopic bone formed in a rodent model of HO, with no effect on the adjacent skeletal bone. This study demonstrates the potential of localized dissolution as a new treatment ​and an alternative to surgery ​for pathological ossification and calcification conditions.

KW - Ectopic bone

KW - Alginate

KW - Biomaterial

KW - Polyphosphate

KW - Targeted delivery

U2 - 10.1016/j.mtbio.2020.100059

DO - 10.1016/j.mtbio.2020.100059

M3 - Article

C2 - 32613185

VL - 7

JO - Materials today. Bio

JF - Materials today. Bio

SN - 2590-0064

M1 - 100059

ER -