Local treatment of experimental mandibular osteomyelitis with an injectable biomimetic gentamicin hydrogel using a new rabbit model

J Biomed Mater Res B Appl Biomater. 2021 Nov;109(11):1677-1688. doi: 10.1002/jbm.b.34824. Epub 2021 Mar 21.

Abstract

Mandibular osteomyelitis (OM) is a challenging disease. Our objective was to assess a new OM model in rabbits induced by arsenic trioxide and to assess the efficacy of local treatment of OM using injectable gentamicin-collagen hydrogels (GNT-COLL). OM was induced unilaterally by controlled confinement of arsenic trioxide paste to the root canal of lower incisors of rabbits, while OM progression was characterized for 16 weeks. On the other hand, two injectable COLL hydrogels functionalized with GNT were prepared and characterized for physicochemical properties; a simple GNT-COLL and a nanohydroxyapatite (nHA)- loaded hydrogel (GNT-COLL/nHA). The two hydrogels were evaluated to treat OM model, while a multidose intramuscular GNT solution served as positive control. Outcomes were assessed by standard methods at 4 and 12 weeks post-surgery. The clinical, radiographical, and histopathological findings provided evidence for the validity of the arsenic-induced OM. The results demonstrated that a single intra-lesional injection of the two hydrogels was more suppressive to OM compared to multidose systemic GNT. The composite GNT-COLL/nHA hydrogel proved to induce early preservation of alveolar bone (ridge) length and higher amount of bone area\total area at 4 weeks (40.53% ± 2.34) followed by GNT-COLL (32.21% ± 0.72). On the other hand, the positive control group revealed the least ridge length and bone area\total area (26.22% ± 1.32) at 4 weeks. Both hydrogels successfully arrested OM with no signs of recurrence for up to 12 weeks. Therefore, results support the greater advantages of the composite hydrogel as an osteogenic/antibiotic delivery system in OM treatment.

Keywords: arsenic; bone regeneration; collagen; drug delivery; gentamicin; hydroxyapatite; injectable hydrogel; mandibular osteomyelitis; rabbit model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology*
  • Disease Models, Animal
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacology*
  • Gentamicins / chemistry
  • Gentamicins / pharmacology*
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Mandibular Diseases / drug therapy*
  • Mandibular Diseases / metabolism
  • Mandibular Diseases / pathology
  • Osteomyelitis / drug therapy*
  • Osteomyelitis / metabolism
  • Osteomyelitis / pathology
  • Rabbits

Substances

  • Drug Carriers
  • Gentamicins
  • Hydrogels