Intramembranous bone regeneration and implant placement using mechanical femoral marrow ablation: rodent models

Abstract

In this paper, we provide a detailed protocol for a model of long bone mechanical marrow ablation in the rodent, including surgical procedure, anesthesia, and pre-and post-operative care. In addition, frequently used experimental end points are briefly discussed. This model was developed to study intramembranous bone regeneration following surgical disruption of the marrow contents of long bones. In this model, the timing of the appearance of bone formation and remodeling is well-characterized and therefore the model is well-suited to evaluate the in vivo effects of various agents which influence these processes. When biomaterials such as tissue engineering scaffolds or metal implants are placed in the medullary cavity after marrow ablation, end points relevant to tissue engineering and implant fixation can also be analyzed. By sharing a detailed protocol, we hope to improve inter-laboratory reproducibility.

How faithfully does intramembranous bone regeneration recapitulate embryonic skeletal development?

“…In models of bone marrow ablation, the marrow and trabecular bone in long bones are mechanically disrupted and removed while the cortical bone remains intact. 43 The wellcharacterized phases of intramembranous bone repair than ensue. 44 in vivo compressive loading of long bones has been used to simulate stress fracture healing in animals which also induces intramembranous bone formation.…”

“…Then, the intramembranous bone which has formed is allowed to mature/remodel with no distraction applied (consolidation phase). In models of bone marrow ablation, the marrow and trabecular bone in long bones are mechanically disrupted and removed while the cortical bone remains intact 43 . The well‐characterized phases of intramembranous bone repair than ensue 44 .…”

The gut microbiota may be a novel pathogenic mechanism in loosening of orthopedic implants in rats

“…We are reporting results from three separate experiments using an established rat model of osteolysis. 39,55 Sample sizes for all experiments were determined by a priori power calculations for the primary bone endpoint, implant fixation strength, which suggested n = 9 rats per study group (β = 0.80, α = 0.05, PS Power and Sample Size Calculation, Nashville, TN). All rats were male and pair-housed in a facility maintained at 22°C and 35%-55% humidity with a 12hour light/dark cycle (light 7 am-7 pm) at Rush University Medical Center (RUMC).…”

“…51,52 Particle-induced osteolysis is a key factor in the failure of orthopedic implants. 50,53,54 In the current series of studies, we utilized a preclinical rat model of particle-induced implant loosening that mimics the human condition of aseptic particle-induced osteolysis ( Figure 1) 39,54,55 to test the hypothesis that implant loosening is associated with disruption of the gut microbiota composition.…”

Intramedullary injury combined with osteoporosis therapeutics regulates targeted local osteogenesis

“…Mechanical bone marrow ablation is one method used to study bone marrow repair 7 . Following bone marrow ablation, the ablated medullary cavity is occupied with reparative trabecular bone and eventually regains bone marrow contents with the disappearance of the reparative trabeculae 8 . To our knowledge, bone marrow ablation is the only method to generate trabecular bone in the diaphyseal marrow cavity.…”