Replacement of an Avulsed Phalanx with Tissue-Engineered Bone

Vacanti, Charles A.; Bonassar, Lawrence J.; Vacanti, Martin P.; Shufflebarger, John

doi:10.1056/nejm200105173442004

Cited by 287 publications

(167 citation statements)

References 35 publications

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“…Periosteal cells have been widely used in bone tissue engineering by isolating osteoprogenitor cells from the patient's periosteum and seeding them into bioresorbable scaffolds [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Fetal bone cells for tissue engineering

Montjovent

Burri

Mark

et al. 2004

Bone

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We envision the use of human fetal bone cells for engineered regeneration of adult skeletal tissue. A description of their cellular function is then necessary. To our knowledge, there is no description of human primary fetal bone cells treated with differentiation factors. The characterization of fetal bone cells is particularly important as the pattern of secreted proteins from osteoblasts has been shown to change during aging. In the first part of this work, human primary fetal bone cells were compared to adult bone cells and mesenchymal stem cells for their ability to proliferate and to differentiate into osteoblasts in vitro. Cell proliferation, gene expression of bone markers, alkaline phosphatase (ALP) activity, and mineralization were analyzed during a time-course study. In the second part of this paper, bone fetal cells behavior exposed to osteogenic factors is further detailed. The doubling time of fetal bone cells was comparable to mesenchymal stem cells but significantly shorter than for adult bone cells. Gene expression of cbfa-1, ALP, a1 chain of type I collagen, and osteocalcin were upregulated in fetal bone cells after 12 days of treatment, with higher inductions than for adult and mesenchymal stem cells. The increase of ALP enzymatic activity was stronger for fetal than for adult bone cells reaching a maximum at day 10, but lower than for mesenchymal stem cells. Importantly, the mineralization process of bone fetal cells started earlier than adult bone and mesenchymal stem cells. Proliferation of fetal and adult bone cells was increased by dexamethasone, whereas 1a,25-dihydroxyvitamin D 3 did not show any proliferative effect. Mineralization studies clearly demonstrated the presence of calcium deposits in the extracellular matrix of fetal bone cells. Nodule formation and calcification were strongly increased by the differentiation treatment, especially by dexamethasone. This study shows for the first time that human primary fetal bone cells could be of great interest for bone research, due to their fast growth rate and their ability to differentiate into mature osteoblasts. They represent an interesting and promising potential for therapeutic use in bone tissue engineering.

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Section: Introductionmentioning

confidence: 99%

Fetal bone cells for tissue engineering

Montjovent

Burri

Mark

et al. 2004

Bone

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“…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.…”

mentioning

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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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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“…Vacanti et al (2001) reported successful tissue engineering of the distal phalanx, to replace this bone in a patient who suffered partial avulsion of the thumb. However, only 25% of the normal strength was obtained.…”

Section: Treatment Of Bone Lossmentioning

confidence: 99%