In vivo loading increases mechanical properties of scaffold by affecting bone formation and bone resorption rates

Abstract

A successful bone tissue engineering strategy entails producing bone-scaffold constructs with adequate mechanical properties. Apart from the mechanical properties of the scaffold itself, the forming bone inside the scaffold also adds to the strength of the construct. In this study, we investigated the role of in vivo cyclic loading on mechanical properties of a bone scaffold. We implanted PLA/β-TCP scaffolds in the distal femur of six rats, applied external cyclic loading on the right leg, and kept the left leg as a control. We monitored bone formation at 7 time points over 35 weeks using time-lapsed micro-computed tomography (CT) imaging. The images were then used to construct micro-finite element models of bone-scaffold constructs, with which we estimated the stiffness for each sample at all time points. We found that loading increased the stiffness by 60% at 35 weeks. The increase of stiffness was correlated to an increase in bone volume fraction of 18% in the loaded scaffold compared to control scaffold. These changes in volume fraction and related stiffness in the bone scaffold are regulated by two independent processes, bone formation and bone resorption. Using time-lapsed micro-CT imaging and a newly-developed longitudinal image registration technique, we observed that mechanical stimulation increases the bone formation rate during 4-10 weeks, and decreases the bone resorption rate during 9-18 weeks post-operatively. For the first time, we report that in vivo cyclic loading increases mechanical properties of the scaffold by increasing the bone formation rate and decreasing the bone resorption rate.© 2011 Elsevier Inc. All rights reserved. IntroductionThe accepted paradigm in bone tissue engineering is to combine a scaffold with cells and/or growth factors [1][2][3][4][5][6]. The scaffold is used for its osteoconductive properties [7,8] and the cells or growth factors are used for their osteoinductive or osteogenic properties [9,10]. While successful in vivo studies [11,12] and in clinical studies [13], this strategy has difficulties to settle in routine clinical practice. The reasons are manifold but often related to the cost, the stringent regulations established by the regulatory authorities, the specialized infrastructure needed, or the lack of possible reimbursement from health insurances when cells or growth factors are employed.As the use of cells or growth factors is indeed the most difficult element to be included for bone tissue engineering, despite their acknowledged usefulness, we advocate a shift in the bone tissue engineering paradigm. Mechanical loading is an intrinsic stimulation present in the skeleton. It has been demonstrated in numerous in vivo studies to be correlated to bone regulation [14,15]. The in situ mechanical stimulation, if considered in an appropriate way, could then replace the cell and growth factor components of the bone tissue engineering strategy. This new paradigm has been proposed recently [16][17][18]. To support this approach, we have previously shown that controlle...

Predicting the Elastic Properties of Selective Laser Sintered PCL/β-TCP Bone Scaffold Materials Using Computational Modelling

“…Cahill et al found that models based on the designed scaffold geometry over-predicted the scaffold stiffness by up to 147% and that surface roughness is a factor that needs to be accounted for 4 . High resolution finite element meshes have been successfully generated from micro-CT scans giving accurate models of the real geometries of both bone tissue engineering scaffolds 6,10,38,49,50,52,57 and native bone tissue 2,29,40,47,51 .Micromechanics approaches to evaluate the mechanical properties of particle-reinforced composites traditionally use idealised microstructures based on particle distribution and are often modelled under periodic boundary conditions 5 . This approach was used by Eshragi et al to determine the bulk mechanical properties of a PCL/hydroxyapatite SLS scaffold 14 .…”

Translation of Biomechanical Concepts in Bone Tissue Engineering: From Animal Study to Revision Knee Arthroplasty

“…By finding the mechanical stimulus, we design an animal study (Box 2) in which the loading condition in the animal is such that the level of mechanical stimulus in the scaffold is similar to that of the targeted clinical application. Bone formation over time inside the scaffold is obtained by longitudinal micro-CT imaging (Roshan-Ghias, Lambers, et al 2011). In addition, micro-CT imaging provides spatial information on the bone formation in the scaffold.…”

“…Results of the animal study with mechanical stimulus corresponding to that determined in Box 1 have been presented in Roshan-Ghias, Lambers, et al (2011). Briefly, the mechanical stimulation enhanced the bone formation inside the scaffold by 18% after 35 weeks.…”

Computational modelling of ovine critical-sized tibial defects with implanted scaffolds and prediction of the safety of fixator removal

“…Similar methods were employed by Roshan-Ghias et al [13] to generate FE models of a scaffold-callus construct for uniaxial loading simulations. The use of four-point bending tests gives a more complete picture of the mechanical integrity of the scaffold-callus construct [6,11] under the complex loading conditions in-vivo [14] in comparison to the use of uniaxial loading alone.…”