Local injection of a hexametaphosphate formulation reduces heterotopic ossification

Alginate Biomaterial Ectopic bone Polyphosphate Targeted delivery

Journal

Materials today. Bio
ISSN: 2590-0064
Titre abrégé: Mater Today Bio
Pays: England
ID NLM: 101757228

Informations de publication

Date de publication:
Jun 2020
Historique:
received: 23 03 2020
revised: 22 05 2020
accepted: 24 05 2020
entrez: 3 7 2020
pubmed: 3 7 2020
medline: 3 7 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 32613185
doi: 10.1016/j.mtbio.2020.100059
pii: S2590-0064(20)30019-3
pii: 100059
pmc: PMC7322360
doi:

Types de publication

Journal Article

Langues

eng

Pagination

100059

Informations de copyright

© 2020 The Author(s).

Déclaration de conflit d'intérêts

The authors have no competing interests to declare.

Références

AAPS PharmSciTech. 2016 Dec;17(6):1508
pubmed: 27417224
Nat Med. 2011 Apr;17(4):454-60
pubmed: 21460849
Meat Sci. 2018 May;139:35-43
pubmed: 29367120
J Mater Sci Mater Med. 2015 Jun;26(6):201
pubmed: 26123234
J Musculoskelet Neuronal Interact. 2014 Mar;14(1):19-28
pubmed: 24583537
Medicine (Baltimore). 2015 May;94(18):e828
pubmed: 25950691
Skeletal Radiol. 2005 Oct;34(10):609-19
pubmed: 16132978
Biomaterials. 2004 May;25(11):2187-95
pubmed: 14741634
Injury. 2013 Apr;44(4):570-5
pubmed: 23398900
Adv Healthc Mater. 2020 Mar;9(5):e1901521
pubmed: 31977153
Sci Transl Med. 2014 Sep 24;6(255):255ra132
pubmed: 25253675
Arch Phys Med Rehabil. 2014 Sep;95(9):1710-3
pubmed: 24685387
J Mater Chem B. 2016 Jun 7;4(21):3815-3822
pubmed: 32263319
J Burn Care Rehabil. 1986 Jul-Aug;7(4):323-7
pubmed: 3117800
J Bone Joint Surg Am. 2007 Mar;89(3):476-86
pubmed: 17332095
Am J Physiol. 1961 Jun;200:1296-300
pubmed: 13700202
Radiother Oncol. 2015 Jul;116(1):4-9
pubmed: 26163090
J Burn Care Res. 2015 Jul-Aug;36(4):465-70
pubmed: 25526176
Antimicrob Agents Chemother. 1989 Oct;33(10):1741-7
pubmed: 2511800
Am J Sports Med. 2014 Jun;42(6):1359-64
pubmed: 24664136
J Bone Joint Surg Br. 2003 Jul;85(5):700-5
pubmed: 12892193
Int Orthop. 2016 Sep;40(9):1967-73
pubmed: 26611728
J Am Acad Orthop Surg. 2004 Mar-Apr;12(2):116-25
pubmed: 15089085
Bone. 2018 Apr;109:134-142
pubmed: 28855144
J Bone Joint Surg Am. 2010 Sep 1;92(11):2032-8
pubmed: 20810853
Bone Joint Res. 2012 Aug 01;1(8):192-7
pubmed: 23610689
J Orthop Res. 2017 Nov;35(11):2397-2406
pubmed: 28390182
Toxicology. 2009 Apr 28;258(2-3):148-56
pubmed: 19428934
Adv Colloid Interface Sci. 2009 Mar-Jun;147-148:214-27
pubmed: 19012872
Bone. 2018 Apr;109:43-48
pubmed: 28455214
Radiother Oncol. 1999 Jun;51(3):197-203
pubmed: 10435813
Biomacromolecules. 2007 Aug;8(8):2533-41
pubmed: 17591747
J Arthroplasty. 2017 Apr;32(4):1328-1334
pubmed: 27884418
Am J Physiol. 1966 Sep;211(3):821-5
pubmed: 4288875
J Orthop Trauma. 2016 Oct;30 Suppl 3:S27-S30
pubmed: 27661424
Environ Sci Technol. 2010 Feb 15;44(4):1260-6
pubmed: 20099802
Bone. 2010 Feb;46(2):425-31
pubmed: 19735753
J Dent. 2014 Mar;42(3):256-62
pubmed: 24333957
J Bone Joint Surg Am. 2015 Jul 1;97(13):1101-11
pubmed: 26135077
Adv Healthc Mater. 2016 Mar 9;5(5):507-28
pubmed: 26789418
Caries Res. 1983;17(3):229-41
pubmed: 6573964

Auteurs

T E Robinson (TE)

Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.
Royal Centre for Defence Medicine, Birmingham Research Park, Vincent Drive, Edgbaston, B15 2SQ, UK.

N M Eisenstein (NM)

Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.
Royal Centre for Defence Medicine, Birmingham Research Park, Vincent Drive, Edgbaston, B15 2SQ, UK.

S C Cox (SC)

Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.

R J A Moakes (RJA)

Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.

A M Thompson (AM)

Neuroscience and Opthalmology, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, B15 2TT, UK.

Z Ahmed (Z)

Neuroscience and Opthalmology, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, B15 2TT, UK.

E A B Hughes (EAB)

Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.
NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Edgbaston, B15 2TH, UK.

L J Hill (LJ)

School of Biomedical Sciences, Institute of Clinical Sciences, University of Birmingham, Edgbaston, B15 2TT, UK.

S A Stapley (SA)

Royal Centre for Defence Medicine, Birmingham Research Park, Vincent Drive, Edgbaston, B15 2SQ, UK.

L M Grover (LM)

Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.

Classifications MeSH