Bone morphogenetic proteins − 7 and − 2 in the treatment of delayed osseous union secondary to bacterial osteitis in ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-07-27

AUTHORS

Lars Helbig, Georg W. Omlor, Adriana Ivanova, Thorsten Guehring, Robert Sonntag, J. Philippe Kretzer, Susann Minkwitz, Britt Wildemann, Gerhard Schmidmaier

ABSTRACT

BackgroundBone 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.MethodsAfter 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.ResultsBiomechanical 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.ConclusionsIn 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. More... »

PAGES

261

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12891-018-2203-7

DOI

http://dx.doi.org/10.1186/s12891-018-2203-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105865417

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30049273


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26 schema:description BackgroundBone 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.MethodsAfter 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.ResultsBiomechanical 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.ConclusionsIn 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.
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34 K-wires
35 Micro-CT analysis
36 Sprague-Dawley rats
37 Staphylococcus aureus
38 Union
39 aim
40 analysis
41 area
42 aureus
43 bacteria inoculation
44 biomechanical testing
45 bone
46 bone consolidation
47 bone healing
48 bone morphogenetic protein
49 bone substitute
50 callus
51 callus formation
52 callus tissue
53 canal
54 challenges
55 chronic infection
56 complex fractures
57 consolidation
58 control
59 control group
60 damage
61 differences
62 efficacy
63 extensive soft tissue damage
64 findings
65 formation
66 fracture healing
67 fracture torque
68 fractured bone
69 fractures
70 great challenge
71 group
72 healing
73 healing efficacy
74 histological findings
75 histomorphometric analysis
76 histomorphometric results
77 impact
78 infected control group
79 infected group
80 infection
81 inoculation
82 intramedullary inoculation
83 irrigation
84 mechanical stability
85 medullary canal
86 micro-CT
87 midshaft tibia
88 mineralized areas
89 model
90 morphogenetic proteins
91 non-infected control group
92 non-infected group
93 ongoing infection
94 open fractures
95 orthopedics
96 osseous union
97 osteitis
98 present rat model
99 prevalence
100 protein
101 quantitative micro-CT
102 randomization
103 rat model
104 rats
105 results
106 rhBMP-2
107 rhBMP-7
108 saline
109 scores
110 second surgery
111 significant differences
112 situation
113 soft tissue damage
114 stability
115 stabilization
116 sterile saline
117 study
118 substitute
119 surgery
120 testing
121 tibia
122 tissue
123 titanium K-wires
124 torque
125 transverse fractures
126 trauma surgery
127 treatment
128 types
129 underwent biomechanical testing
130 weeks
131 weeks rats
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