Differential fracture healing resulting from fixation stiffness variability: a mouse model

Abstract

Background The mechanisms underlying the interaction between the local mechanical environment and fracture healing are not known. We developed a mouse femoral fracture model with implants of different stiffness, and hypothesized that differential fracture healing would result. Methods Femoral shaft fractures were created in 70 mice, and were treated with an intramedullary nail made of either tungsten (Young’s modulus = 410 GPa) or aluminum (Young’s modulus = 70 GPa). Mice were then sacrificed at two weeks or five weeks. Fracture calluses were analyzed using standard microCT, histological, and biomechanical methods. Results At two weeks, callus volume was significantly greater in the aluminum group compared to the tungsten group (61.2 mm3 vs 40.5 mm3; p = 0.016), yet bone volume within the calluses was no different between the groups (13.2 mm3 vs 12.3 mm3). Calluses from the tungsten group were more stiff on mechanical testing (18.7 N/mm vs 9.7 N/mm, p = 0.01). The percent cartilage in the callus was 31.6% in the aluminum group and 22.9% in the tungsten group (p = 0.40). At 5 weeks, there were no differences between any of the healed femora. Conclusions In this study, fracture implants with different stiffnesses led to differential fracture healing in this mouse fracture model. Fractures treated with a stiffer implant had more advanced healing at two weeks, but still healed by callus formation. Although this concept has been well documented previously, this particular model could provide a valuable research tool to study the healing consequences of altered fixation stiffness, which may provide insight into the pathogenesis and ideal treatment of fractures and nonunions.

What Are the Biomechanical Properties of the Taylor Spatial Frame™?

“…To comment meaningfully how this knowledge may be applied to clinical practice, a current understanding of the biomechanics of bone healing must be considered. There is general consensus that a certain level of axial strain is desirable and necessary to stimulate bone healing with, among others, Kenwright and Goodship [22], as early as 1989, reporting increased callus mineralization and fracture stiffness in ovine tibial fractures with approximately 16% axial strain compared with more rigid fixation, although this was seen to deteriorate in quality somewhat with increased strains of up to 66% [10,13,17,22,34,36]. Likewise, although there is less agreement on this, it generally is considered that shear strain, whether linear or rotational, is detrimental to bone healing and should be limited where possible [3,8,10,29,36].…”

The association between mineralised tissue formation and the mechanical local in vivo environment: Time-lapsed quantification of a mouse defect healing model

“…Additionally, reconciling the wide range of densities that are observed during the fracture healing process is key to improve micro-FE prediction of mechanical stimuli. Traditionally, either single absolute thresholds, ranging from 394.8 to 641 mg HA/cm 3 24-26 (HA: hydroxyapatite); or relative thresholds based on percentages of grey values; such as 25% to 33% [27][28][29] have been used to segment bone. We improve upon these approaches via the use of a "multi-density threshold approach", whereby we apply a range of thresholds to identify the spatially and temporally changing densities of bone, allowing us to quantify local mineralisation kinetics and reconcile the range of bone densities within the healing environment.…”

Biomechanical Testing of a Calcium Phosphate-Phosphoserine–Based Mineral-Organic Adhesive for Non-invasive Fracture Repair of Mandibular Fractures in Dogs

“…Stiffness is an important consideration in fracture repair in order to achieve direct bone healing (35). A lack of stiffness may reduce relative stability and hence negatively impact the potential for direct bone healing.…”

“…For this study, the rate of displacement was fixed and directly related to time. Stiffer materials would be more appropriate for primary bone healing by stabilizing and protecting the fracture site and have been shown to ensure more advanced healing at the same time point (35). The relative flexibility of bone likely contributed to no differences between stiffnesses when comparing groups (36).…”