Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering

Montjovent, Marc-Olivier; Mark, Silke; Mathieu, Laurence; Scaletta, Corinne; Scherberich, Arnaud; Delabarde, Claire; Zambelli, Pierre‐Yves; Bourban, P.-E.; Applegate, Lee Ann; Pioletti, Dominique P.

doi:10.1016/j.bone.2007.10.018

Cited by 75 publications

(53 citation statements)

References 42 publications

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“…In each leg, a hole of 3 mm in diameter and height was made using a metal drill bit on the lateral side of the distal femur underneath the growth plate. Afterwards, PLA/5wt.% β-TCP scaffolds (80% porous) [26] of the same size were implanted inside the holes [10]. No cells or growth factors were added in the scaffold.…”

Section: Surgerymentioning

confidence: 99%

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

Roshan-Ghias¹,

Lambers²,

Gholam‐Rezaee³

et al. 2011

Bone

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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...

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Section: Surgerymentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Roshan-Ghias¹,

Lambers²,

Gholam‐Rezaee³

et al. 2011

Bone

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“…It involves migration of several cell types [1], proliferation [2], differentiation [3], angiogenesis [4,5], and mineralization [6], as well as the interaction of numerous cytokines and growth factors [7]. Bone formation also depends on the architecture of the scaffold [8], its surface properties [9], the mechanical stimulation [10,11], the implantation site [12], and the boneescaffold interface [13]. Probing the effects of each parameter and their interaction has proven challenging.…”

Section: Introductionmentioning

confidence: 99%

Prediction of spatio-temporal bone formation in scaffold by diffusion equation

et al. 2011

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a b s t r a c tDeveloping 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, a, 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.

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“…However, presently, the developments for artificial bone implants performed with human fetal cells have used materials that were designed to be biodegradable. [10][11][12] In the present study, our goals were to develop calcium aluminate scaffolds suitable for permanent bone replacement, displaying an open-porous channel microstructure allowing the engraftment and migration through the ceramics of human histocompatible bone-derived cells. The calcium aluminate scaffolds were produced from a modified direct foaming method [13][14][15][16][17][18][19] which allows the production of macroporous scaffolds which are tailorable in pore size, microstructure and shape.…”

Section: Introductionmentioning

confidence: 99%

Functionalization of Microstructured Open-Porous Bioceramic Scaffolds with Human Fetal Bone Cells

et al. 2012

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Bone substitute materials permissive for trans-scaffold migration and in-scaffold survival of human bone-derived cells are mandatory to develop cell-engineered permanent implants to repair bone defects. In this study, we evaluated the influence on human bone-derived cells of the material composition and microstructure of foam scaffolds made from calcium aluminate using a direct foaming method allowing wide-range tailoring of the microstructure for pore size and pore openings. Human fetal osteoblasts attached to the scaffolds, migrated across the entire materials depending on the scaffold pore size, colonized and survived in the porous material for at least 6 weeks. The long-term biocompatibility of the scaffold material for human cells was evidenced by in scaffold determination of cell metabolic activity using a modified MTT assay, a repeated WST-1 assay and scanning electron microscopy. Finally, we demonstrated that the fetal cells can be covalently bound to the scaffolds using biocompatible click chemistry, thus enhancing the rapid adhesion of the cells to the scaffolds. Thus, the different microstructures of the foams influenced the migratory potential of the cells, but not cell viability, and the scaffolds were permissive for covalent biocompatible chemical binding of the cells to the materials, allowing either localized or widespread cellularization of the scaffolds for cell-engineered implants.

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Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering

Cited by 75 publications

References 42 publications

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

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

Prediction of spatio-temporal bone formation in scaffold by diffusion equation

Functionalization of Microstructured Open-Porous Bioceramic Scaffolds with Human Fetal Bone Cells

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