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...