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BMC Musculoskelet Disord. 2018 Jul 27;19(1):261. doi: 10.1186/s12891-018-2203-7.

Bone morphogenetic proteins - 7 and - 2 in the treatment of delayed osseous union secondary to bacterial osteitis in a rat model.

Author information

1
Clinic for Orthopedics and Trauma Surgery, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, 69118, Heidelberg, Germany.
2
Clinic for Orthopedics and Trauma Surgery, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, 69118, Heidelberg, Germany. Georg.omlor@med.uni-heidelberg.de.
3
Clinic for Trauma and Orthopaedic Surgery, BG Trauma Center Ludwigshafen at Heidelberg University Hospital, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen on the Rhine, Germany.
4
Laboratory of Biomechanics and Implant Research, Clinic for Orthopedics and Trauma Surgery, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, 69118, Heidelberg, Germany.
5
Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, 13353, Berlin, Germany.
6
Experimental Trauma Surgery, Universitätsklinikum Jena, 07747, Jena, Germany.

Abstract

BACKGROUND:

Bone infections due to trauma and subsequent delayed or impaired fracture healing represent a great challenge in orthopedics and trauma surgery. The prevalence of such bacterial infection-related types of delayed non-union is high in complex fractures, particularly in open fractures with additional extensive soft-tissue damage. The aim of this study was to establish a rat model of delayed osseous union secondary to bacterial osteitis and investigate the impact of rhBMP-7 and rhBMP-2 on fracture healing in the situation of an ongoing infection.

METHODS:

After randomization to four groups 72 Sprague-Dawley rats underwent a transverse fracture of the midshaft tibia stabilized by intramedullary titanium K-wires. Three groups received an intramedullary inoculation with Staphylococcus aureus (103 colony-forming units) before stabilization and the group without bacteria inoculation served as healing control. After 5 weeks, a second surgery was performed with irrigation of the medullary canal and local rhBMP-7 and rhBMP-2 treatment whereas control group and infected control group received sterile saline. After further 5 weeks rats were sacrificed and underwent biomechanical testing to assess the mechanical stability of the fractured bone. Additional micro-CT analysis, histological, and histomorphometric analysis were done to evaluate bone consolidation or delayed union, respectively, and to quantify callus formation and the mineralized area of the callus.

RESULTS:

Biomechanical testing showed a significantly higher fracture torque in the non-infected control group and the infected rhBMP-7- and rhBMP-2 group compared with the infected control group (p < 0.001). RhBMP-7 and rhBMP-2 groups did not show statistically significant differences (p = 0.57). Histological findings supported improved bone-healing after rhBMP treatment but quantitative micro-CT and histomorphometric results still showed significantly more hypertrophic callus tissue in all three infected groups compared to the non-infected group. Results from a semiquantitative bone-healing-score revealed best bone-healing in the non-infected control group. The expected chronic infection was confirmed in all infected groups.

CONCLUSIONS:

In delayed bone healing secondary to infection rhBMP treatment promotes bone healing with no significant differences in the healing efficacy of rhBMP-2 and rhBMP-7 being noted. Further new therapeutic bone substitutes should be analyzed with the present rat model for delayed osseous union secondary to bacterial osteitis.

KEYWORDS:

Animal model; Biomechanical testing; Bone morphogenetic protein 2; Bone morphogenetic protein 7; Delayed osseous union; Micro-CT; Osteitis; Rat

PMID:
30049273
PMCID:
PMC6062917
DOI:
10.1186/s12891-018-2203-7
[Indexed for MEDLINE]
Free PMC Article

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