In Vivo Quantification and Mathematical Description of Osteogenesis in Tissue Engineering Scaffold

INTRODUCTION Developing a successful bone tissue engineering strategy entails translation of experimental findings to clinical needs. A major leap forward towards this goal is a quantitative tool to predict spatial and temporal bone formation in scaffold. We hypothesized that bone formation in an osteoconductive scaffold follows diffusion phenomenon. In order to identify the proposed model, we implanted PLA/β-TCP scaffolds in distal femur of rats and measured bone formation using longitudinal micro-CT imaging. We then validated the proposed model using two other published in vivo models

Mathematical modeling of bone formation inside tissue engineering scaffolds (Master project)

Tissue engineering scaffolds are porous structures that allow bone cells to reside and produce bone. This process involves migration and differentiation of mesenchymal stromal cells and production of cartilage and bone by chondrocytes and osteoblasts, which is basically a bone healing process. Based on a mechanistic model of fracture healing, a 2D model of bone formation inside scaffold will be developed. Extensive experimental data from an in vivo study is available which will be used to verify the results of this mathematical model. This project demands working with MATLAB and COMSOL. A good mathematical background is highly recommended

In vivo cyclic loading as a potent stimulatory signal for bone formation inside tissue engineering scaffold

In clinical situations, bone defects are often located at load bearing sites. Tissue engineering scaffolds are future bone substitutes and hence they will be subjected to mechanical stimulation. The goal of this study was to test if cyclic loading can be used as stimulatory signal for bone formation in a bone scaffold. Poly(L-lactic acid) (PLA)/ 5% beta-tricalcium phosphate (beta-TCP) scaffolds were implanted in both distal femoral epiphyses of eight rats. Right knees were stimulated (10N, 4Hz, 5 min) five times, every two days, starting from the third day after surgery while left knees served as control. Finite element study of the in vivo model showed that the strain applied to the scaffold is similar to physiological strains. Using micro-computed tomography (CT), all knees were scanned five times after the surgery and the related bone parameters of the newly formed bone were quantified. Statistical modeling was used to estimate the evolution of these parameters as a function of time and loading. The results showed that mechanical stimulation had two effects on bone volume (BV): an initial decrease in BV at week 2, and a long-term increase in the rate of bone formation by 28%. At week 13, the BV was then significantly higher in the loaded scaffolds

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

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