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Hydroxyapatite : An Antibiotic Recruiting Moiety for Local Treatment and Prevention of Bone Infections

Sebastian, Sujeesh LU orcid ; Huang, Jintian LU ; Liu, Yang LU ; Tandberg, Felix ; Collin, Mattias LU orcid ; Puthia, Manoj LU and Raina, Deepak Bushan LU (2024) In Journal of Orthopaedic Research 42(1). p.212-222
Abstract

Treatment of chronic osteomyelitis by radical debridement and filling of the dead space with antibiotic containing calcium sulphate/hydroxyapatite (CaS/HA) bone substitute has shown excellent long-term outcomes. However, in extensive infections, sessile bacteria may remain in bone cells or soft tissues protected by biofilm leading to recurrences. The primary aim of this study was to evaluate if systemically administrated tetracycline (TET) could bind to pre-implanted HA particles and impart an anti-bacterial effect locally. In-vitro studies indicated that the binding of TET to nano- and micro-sized HA particles was rapid and plateaued already at 1 h. Since protein passivation of HA after in-vivo implantation could affect HA-TET... (More)

Treatment of chronic osteomyelitis by radical debridement and filling of the dead space with antibiotic containing calcium sulphate/hydroxyapatite (CaS/HA) bone substitute has shown excellent long-term outcomes. However, in extensive infections, sessile bacteria may remain in bone cells or soft tissues protected by biofilm leading to recurrences. The primary aim of this study was to evaluate if systemically administrated tetracycline (TET) could bind to pre-implanted HA particles and impart an anti-bacterial effect locally. In-vitro studies indicated that the binding of TET to nano- and micro-sized HA particles was rapid and plateaued already at 1 h. Since protein passivation of HA after in-vivo implantation could affect HA-TET interaction, we investigated the effect of serum exposure on HA-TET binding in an antibacterial assay. Although, serum exposure reduced the zone of inhibition (ZOI) of Staphylococcus aureus, a significant ZOI could still be observed after pre-incubation of HA with serum. We could in addition show that zoledronic acid (ZA) competes for the same binding sites as TET and that exposure to high doses of ZA led to reduced TET-HA binding. In an in-vivo setting, we then confirmed that systemically administered TET seeks HA particles which were pre-implanted in a muscle and subcutaneous pouches in rats and mice respectively, preventing HA particles from being colonized by S. aureus. Clinical Significance: This study describes a new drug delivery method which could prevent bacterial colonization of a HA biomaterial and reduce recurrences in bone infection. This article is protected by copyright. All rights reserved.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Orthopaedic Research
volume
42
issue
1
pages
212 - 222
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85164135282
  • pmid:37334776
ISSN
1554-527X
DOI
10.1002/jor.25650
language
English
LU publication?
yes
additional info
This article is protected by copyright. All rights reserved.
id
53b191f0-434c-43e5-a19d-a1085a625abf
date added to LUP
2023-06-19 14:14:06
date last changed
2024-04-20 01:55:05
@article{53b191f0-434c-43e5-a19d-a1085a625abf,
  abstract     = {{<p>Treatment of chronic osteomyelitis by radical debridement and filling of the dead space with antibiotic containing calcium sulphate/hydroxyapatite (CaS/HA) bone substitute has shown excellent long-term outcomes. However, in extensive infections, sessile bacteria may remain in bone cells or soft tissues protected by biofilm leading to recurrences. The primary aim of this study was to evaluate if systemically administrated tetracycline (TET) could bind to pre-implanted HA particles and impart an anti-bacterial effect locally. In-vitro studies indicated that the binding of TET to nano- and micro-sized HA particles was rapid and plateaued already at 1 h. Since protein passivation of HA after in-vivo implantation could affect HA-TET interaction, we investigated the effect of serum exposure on HA-TET binding in an antibacterial assay. Although, serum exposure reduced the zone of inhibition (ZOI) of Staphylococcus aureus, a significant ZOI could still be observed after pre-incubation of HA with serum. We could in addition show that zoledronic acid (ZA) competes for the same binding sites as TET and that exposure to high doses of ZA led to reduced TET-HA binding. In an in-vivo setting, we then confirmed that systemically administered TET seeks HA particles which were pre-implanted in a muscle and subcutaneous pouches in rats and mice respectively, preventing HA particles from being colonized by S. aureus. Clinical Significance: This study describes a new drug delivery method which could prevent bacterial colonization of a HA biomaterial and reduce recurrences in bone infection. This article is protected by copyright. All rights reserved.</p>}},
  author       = {{Sebastian, Sujeesh and Huang, Jintian and Liu, Yang and Tandberg, Felix and Collin, Mattias and Puthia, Manoj and Raina, Deepak Bushan}},
  issn         = {{1554-527X}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{212--222}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Orthopaedic Research}},
  title        = {{Hydroxyapatite : An Antibiotic Recruiting Moiety for Local Treatment and Prevention of Bone Infections}},
  url          = {{http://dx.doi.org/10.1002/jor.25650}},
  doi          = {{10.1002/jor.25650}},
  volume       = {{42}},
  year         = {{2024}},
}