Cyclic mechanical compression increases mineralization of cell-seeded polymer scaffolds in vivo.
ABSTRACT Despite considerable documentation of the ability of normal bone to adapt to its mechanical environment, very little is known about the response of bone grafts or their substitutes to mechanical loading even though many bone defects are located in load-bearing sites. The goal of this research was to quantify the effects of controlled in vivo mechanical stimulation on the mineralization of a tissue-engineered bone replacement and identify the tissue level stresses and strains associated with the applied loading. A novel subcutaneous implant system was designed capable of intermittent cyclic compression of tissue-engineered constructs in vivo. Mesenchymal stem cell-seeded polymeric scaffolds with 8 weeks of in vitro preculture were placed within the loading system and implanted subcutaneously in male Fisher rats. Constructs were subjected to 2 weeks of loading (3 treatments per week for 30 min each, 13.3 N at 1 Hz) and harvested after 6 weeks of in vivo growth for histological examination and quantification of mineral content. Mineralization significantly increased by approximately threefold in the loaded constructs. The finite element method was used to predict tissue level stresses and strains within the construct resulting from the applied in vivo load. The largest principal strains in the polymer were distributed about a modal value of -0.24% with strains in the interstitial space being about five times greater. Von Mises stresses in the polymer were distributed about a modal value of 1.6 MPa, while stresses in the interstitial tissue were about three orders of magnitude smaller. This research demonstrates the ability of controlled in vivo mechanical stimulation to enhance mineralized matrix production on a polymeric scaffold seeded with osteogenic cells and suggests that interactions with the local mechanical environment should be considered in the design of constructs for functional bone repair.
Article: Surgical preparation of bone-scaffold interface is critical for bone regeneration inside tissue engineering scaffold.[show abstract] [hide abstract]
ABSTRACT: The goal of this study was to investigate if the preparation of implantation site affects bone formation inside tissue engineering scaffolds. For this purpose, two different drilling techniques were used to create a hole in distal femurs of rats before the insertion of a bone scaffold: a manually driven wood drill bit and an electrically driven metal drill bit. The size and the position of the hole were identical for the two cases. The bone volume, bone mineral density, and callus formation were assessed noninvasively using micro-CT tomography at several time points after implantation. The formation of bone and soft tissue inside scaffold were evaluated by histology. The bone structure around the holes made by the two techniques was compared ex vivo. The long-term study of bone formation showed that when a wood drill bit was used, the bone formation is accelerated by 3 weeks compared to when a metal drill bit was used. The ex vivo studies suggest that this result is due to the drilling methods differentially affecting the structure of the bone surrounding the generated defects.Journal of Orthopaedic Research 05/2011; 29(5):767-72. · 2.81 Impact Factor
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ABSTRACT: Developing a successful bone tissue engineering strategy entails translation of experimental findings to clinical needs. A major leap forward toward this goal is developing a quantitative tool to predict spatial and temporal bone formation in scaffold. We hypothesized that bone formation in scaffold follows diffusion phenomenon. Subsequently, we developed an analytical formulation for bone formation, which had only three unknown parameters: C, the final bone volume fraction, α, the so-called scaffold osteoconduction coefficient, and h, the so-called peri-scaffold osteoinduction coefficient. The three parameters were estimated by identifying the model within vivo data of polymeric scaffolds implanted in the femoral condyle of rats. In vivo data were obtained by longitudinal micro-CT scanning of the animals. Having identified the three parameters, we used the model to predict the course of bone formation in two previously published in vivo studies. We found the predicted values to be consistent with the experimental ones. Bone formation into a scaffold can then adequately be described through diffusion phenomenon. This model allowed us to spatially and temporally predict the outcome of tissue engineering scaffolds with only 3 physically relevant parameters.Biomaterials 06/2011; 32(29):7006-12. · 7.40 Impact Factor
Article: In vivo loading increases mechanical properties of scaffold by affecting bone formation and bone resorption rates.[show abstract] [hide abstract]
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.Bone 09/2011; 49(6):1357-64. · 4.02 Impact Factor