Local application of a gentamicin-loaded thermo-responsive hydrogel allows for fracture healing upon clearance of a high Staphylococcus aureus load in a rabbit model

G. J.A. ter Boo, T. Schmid, I. Zderic, D. Nehrbass, K. Camenisch, R. G. Richards, D. W. Grijpma, T. F. Moriarty, D. Eglin (Corresponding Author)

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Abstract

Antibiotic-loaded biomaterials (ALBs) have emerged as a potentially useful adjunctive antimicrobial measure for the prevention of infection in open fracture care. A biodegradable thermo-responsive poly(N-isopropylacrylamide) grafted hyaluronic acid (HApN) hydrogel loaded with gentamicin has recently been shown to prevent implant-related infection in a rabbit osteosynthesis model. The primary aim of this study was to determine the influence of this HApN hydrogel on bone healing at an early stage (4 weeks). A rabbit humeral osteotomy model with plating osteosynthesis was used to compare fracture healing in rabbits receiving the hydrogel as compared with control animals. The secondary aim was to observe fracture healing in groups treated with and without antibiotic-loaded hydrogel in the presence of bacterial contamination. In all groups, outcome measures were mechanical stability and histological score, with additional quantitative bacteriology in the inoculated groups. Application of the HApN hydrogel in non-inoculated rabbits did not significantly influence humeral stiffness or histological scores for fracture healing in comparison to controls. In the inoculated groups, animals receiving the bacterial inoculum without hydrogel were culture-positive at euthanasia and found to display lower humeral stiffness values and higher histopathological scores for bacterial presence in comparison with equivalents receiving the gentamicin-loaded HApN hydrogel, which were also infection-free. In summary, our data showed that HApN was an effective antibiotic carrier that did not affect fracture healing. This data supported its suitability for application in fracture care. Addition of osteopromotive compounds could provide further support for accelerating fracture healing in addition to successful infection prophylaxis.

Original languageEnglish
Pages (from-to)151-164
Number of pages14
JournalEuropean Cells and Materials
Volume35
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Fracture Healing
Hydrogel
Gentamicins
Hydrogels
Staphylococcus aureus
Rabbits
Antibiotics
Anti-Bacterial Agents
Infection
Bacteriology
Animals
Stiffness
Hyaluronic acid
Open Fractures
Euthanasia
Mechanical stability
Biocompatible Materials
Hyaluronic Acid
Osteotomy
Plating

Keywords

  • Biomaterial-associated infection
  • Fracture healing
  • Prophylaxis
  • Staphylococcus aureus
  • Thermo-responsive hydrogel

Cite this

ter Boo, G. J.A. ; Schmid, T. ; Zderic, I. ; Nehrbass, D. ; Camenisch, K. ; Richards, R. G. ; Grijpma, D. W. ; Moriarty, T. F. ; Eglin, D. / Local application of a gentamicin-loaded thermo-responsive hydrogel allows for fracture healing upon clearance of a high Staphylococcus aureus load in a rabbit model. In: European Cells and Materials. 2018 ; Vol. 35. pp. 151-164.
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abstract = "Antibiotic-loaded biomaterials (ALBs) have emerged as a potentially useful adjunctive antimicrobial measure for the prevention of infection in open fracture care. A biodegradable thermo-responsive poly(N-isopropylacrylamide) grafted hyaluronic acid (HApN) hydrogel loaded with gentamicin has recently been shown to prevent implant-related infection in a rabbit osteosynthesis model. The primary aim of this study was to determine the influence of this HApN hydrogel on bone healing at an early stage (4 weeks). A rabbit humeral osteotomy model with plating osteosynthesis was used to compare fracture healing in rabbits receiving the hydrogel as compared with control animals. The secondary aim was to observe fracture healing in groups treated with and without antibiotic-loaded hydrogel in the presence of bacterial contamination. In all groups, outcome measures were mechanical stability and histological score, with additional quantitative bacteriology in the inoculated groups. Application of the HApN hydrogel in non-inoculated rabbits did not significantly influence humeral stiffness or histological scores for fracture healing in comparison to controls. In the inoculated groups, animals receiving the bacterial inoculum without hydrogel were culture-positive at euthanasia and found to display lower humeral stiffness values and higher histopathological scores for bacterial presence in comparison with equivalents receiving the gentamicin-loaded HApN hydrogel, which were also infection-free. In summary, our data showed that HApN was an effective antibiotic carrier that did not affect fracture healing. This data supported its suitability for application in fracture care. Addition of osteopromotive compounds could provide further support for accelerating fracture healing in addition to successful infection prophylaxis.",
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Local application of a gentamicin-loaded thermo-responsive hydrogel allows for fracture healing upon clearance of a high Staphylococcus aureus load in a rabbit model. / ter Boo, G. J.A.; Schmid, T.; Zderic, I.; Nehrbass, D.; Camenisch, K.; Richards, R. G.; Grijpma, D. W.; Moriarty, T. F.; Eglin, D. (Corresponding Author).

In: European Cells and Materials, Vol. 35, 01.01.2018, p. 151-164.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Local application of a gentamicin-loaded thermo-responsive hydrogel allows for fracture healing upon clearance of a high Staphylococcus aureus load in a rabbit model

AU - ter Boo, G. J.A.

AU - Schmid, T.

AU - Zderic, I.

AU - Nehrbass, D.

AU - Camenisch, K.

AU - Richards, R. G.

AU - Grijpma, D. W.

AU - Moriarty, T. F.

AU - Eglin, D.

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AB - Antibiotic-loaded biomaterials (ALBs) have emerged as a potentially useful adjunctive antimicrobial measure for the prevention of infection in open fracture care. A biodegradable thermo-responsive poly(N-isopropylacrylamide) grafted hyaluronic acid (HApN) hydrogel loaded with gentamicin has recently been shown to prevent implant-related infection in a rabbit osteosynthesis model. The primary aim of this study was to determine the influence of this HApN hydrogel on bone healing at an early stage (4 weeks). A rabbit humeral osteotomy model with plating osteosynthesis was used to compare fracture healing in rabbits receiving the hydrogel as compared with control animals. The secondary aim was to observe fracture healing in groups treated with and without antibiotic-loaded hydrogel in the presence of bacterial contamination. In all groups, outcome measures were mechanical stability and histological score, with additional quantitative bacteriology in the inoculated groups. Application of the HApN hydrogel in non-inoculated rabbits did not significantly influence humeral stiffness or histological scores for fracture healing in comparison to controls. In the inoculated groups, animals receiving the bacterial inoculum without hydrogel were culture-positive at euthanasia and found to display lower humeral stiffness values and higher histopathological scores for bacterial presence in comparison with equivalents receiving the gentamicin-loaded HApN hydrogel, which were also infection-free. In summary, our data showed that HApN was an effective antibiotic carrier that did not affect fracture healing. This data supported its suitability for application in fracture care. Addition of osteopromotive compounds could provide further support for accelerating fracture healing in addition to successful infection prophylaxis.

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KW - Prophylaxis

KW - Staphylococcus aureus

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