The investigation of bone fracture healing under intramembranous and endochondral ossification

Abstract

After trauma, fractured bone starts healing directly through bone union or indirectly through callus formation process. Intramembranous and endochondral ossification are two commonly known mechanisms of indirect healing. The present study investigated the bone fracture healing under intramembranous and endochondral ossification by developing theoretical models in conjunction with performing a series of animal experiments. Using experimentally determined mean bone densities in sheep tibia stabilized by the Locking Compression Plate (LCP) fixation system, the research outcomes showed that intramembranous and endochondral ossification can be described by Hill Function with two unique sets of function parameters in mechanical stimuli mediated fracture healing. Two different thresholds exist within the range of mechanical simulation index which could trigger significant intramembranous and endochondral ossification, with a relatively higher bone formation rate of endochondral ossification than that of intramembranous ossification. Furthermore, the increase of flexibility of the LCP system and the use of titanium LCP could potentially promote uniform bone formation across the fracture gap, ultimately better healing outcomes.

Keywords: Bone fracture healing; Endochondral ossification; Intramembranous ossification; Locking compression plate; Mechano-regulation; Titanium.

Fig. 1

(a) A schematic diagram for predicting mechanical stimuli mediated healing under different fixation conditions; and (b) Details of the mechano-regulation model proposed in this study

Fig. 2

(a) A schematic diagram of the Locking compression plate (LCP) system used in this study. The mechanical stiffness can be regulated by adjusting bone plate distance (BPD = 0 mm or 2 mm and defined as the distance between bone and fixation plate) and working length (WL = 35 mm and defined as the distance between two innermost screws); and (b) loading protocol where axial load in sheep tibia is normalized to its Body Weight (BW) and is assumed to increase linearly as healing progresses (Döbele et al., 2010; Grasa et al., 2010).

Fig. 3

CT imaging of fractured bone. Mean bone density was evaluated in the area located in near cortex and far cortex by using Hounsfield unit (HU).

Fig. 4

Comparison of the numerical predictions to the animal experimental data. It can be seen that the experimental results are described remarkably well by numerical results using optimized model parameters.

Fig. 5

Histological evaluations of new bone development using Masson's trichrome staining at 8-weeks after animal sacrifice and removal of the fixation. Arrow 1: new bone; Arrow 2: collagen.

Fig. 6

Rate of relative degree of calcification (per week) induced by mechanical stimulation in intramembranous ossification (0 < S ≤ 1) and endochondral ossification (1 < S ≤ 3). It is assumed that the excessive S (S > 3) will lead to non-union.

Fig. 7

Percent increase in degree of calcification as a function of time post-operation (weeks) by using titanium LCP relative to the control (i.e. Stainless steel LCP).

Fig. 8

Sensitivity analysis of the total bone formation rate (B_p) on depending parameters: basal bone formation rate (B_p0), new bone formation rate (λ), steepness of Hill's function (n), mechanical stimuli index (S) and activation coefficients (K).