A new sequential animal model for infection-related non-unions with segmental bone defect

Abstract

Background: The treatment of fracture-related infections (FRI) is still a challenge for orthopedic surgeons. The prevalence of FRI is particularly high in open fractures with extensive soft-tissue damage. This study aimed to develop a new two-step animal model for non-unions with segmental bone defects, which could be used to evaluate new innovative bone substitutes to improve the therapeutic options in humans with FRI and bone defects. Methods: After randomization to infected or non-infected groups, 30 Sprague-Dawley rats underwent a transverse osteotomy of the mid-shaft femur with a 5 mm defect. Additionally, the periosteum at the fracture zone was cauterized at both sides. After intramedullary inoculation with 10 3 CFU Staphylococcus aureus (infected group) or PBS (non-infected group), a fracture stabilization was done by intramedullary K-wires. After 5 weeks, the bone healing process was evaluated, and revision surgery was performed in order to obtain increased bone healing. The initial K-wires were removed, and debridement of the osteotomy-gap was done followed by a more stable reosteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and the bone consolidation was tested biomechanically and the callus formation quantitatively by micro-CT analysis. Results: We developed and presented a new two-stage non-union animal model through a targeted S. aureus infection. After 5 weeks, all animals showed a non-union irrespective of assignment to the infected and noninfected group. Lane and Sandhu score showed a higher callus formation in the infected group. In all infected animals, the inoculated S. aureus strain was detected in the revision surgery. The second surgery did not improve bone healing, as shown by the Lane Sandhu score and in the μ-CT analysis. Similarly, biomechanical testing showed in both groups a significantly lower maximum torque as compared to the contralateral side (p < 0.0001). Conclusions: We were able to successfully develop a new two-stage non-union animal model, which reflects a genuine clinical situation of an infection-related non-union model with segmental bone defects. This model could be used to evaluate various therapeutic anti-infectious and osteoinductive strategies in FRIs.

Systemic Administration of PTH Supports Vascularization in Segmental Bone Defects Filled with Ceramic-Based Bone Graft Substitute

“…We employed a two-step non-union animal model [25] to investigate a combinatory treatment of HACaS+G and PTH in addition to the standard surgical treatment of nonunions. Both treatment options, PTH and HACaS+G, have been tested extensively on several orthopedic indications, but to our knowledge, never in a combinatory treatment specifically on a two-step non-union model [11][12][13][14][19][20][21]26].…”

Impact of High-Dose Anti-Infective Agents on the Osteogenic Response of Mesenchymal Stem Cells

“…The surgical therapy of critical size bone defects and bone nonunions presents a great challenge for orthopedic surgeons [1]. Especially, nonunions and defects caused by infections are extremely difficult to treat, sometimes taking months or even years to heal, if at all [2].…”

Treatment of Infection-Related Non-Unions with Bioactive Glass—A Promising Approach or Just Another Method of Dead Space Management?

“…Staphylococcus aureus subsp. aureus ATCC ® 49230™ has already been established in several animal models [ 36 , 37 ]. The agent was cultured in a tryptic soy broth (TSB) at 37 °C with 5% CO 2 under constant shaking (200 rpm).…”

“…Our group has previously established a sequential animal model for infection-related non-unions with segmental bone defects, which allowed the evaluation of therapeutic interventions in a genuine clinical simulation. [ 36 ]. To our knowledge, S53P4 has never been evaluated in a two-stage infectious non-union model.…”