A tissue engineering approach to bone repair in large animal models and in clinical practice

Cancedda, Ranieri; Giannoni, Paolo; Mastrogiacomo, Maddalena

doi:10.1016/j.biomaterials.2007.06.023

Cited by 466 publications

(351 citation statements)

References 100 publications

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“…The bone mineral density and bone strength in sheep is increased relative to human. Moreover, sheep models of critical size defects are extensively applied to evaluate cell-based therapeutic approaches using autologues, allogeneic or xenogeneic MPCs in combination with growth factors and different types of scaffolds to enhance bone regeneration showing significant advantages compared with cell-unloaded (empty) scaffolds [43,53,166,[169][170][171][172][173][174][175][176].…”

Section: Sheepmentioning

confidence: 99%

The rational use of animal models in the evaluation of novel bone regenerative therapies

Perić¹,

Dumić-Čule²,

Grčević³

et al. 2015

Bone

126

116

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Section: Sheepmentioning

confidence: 99%

The rational use of animal models in the evaluation of novel bone regenerative therapies

Perić¹,

Dumić-Čule²,

Grčević³

et al. 2015

Bone

126

116

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“…Orthopaedic or maxillofacial osseous defects typically are repaired by bone transplantation with either autologous graft or nonautologous bone substitutes [4]. Although autologous grafts are considered the gold standard for bone grafts, donor site morbidity is a possible outcome and nonautologous or synthetic bone materials often are preferred by patients and clinicians [5,16,41].…”

Section: Introductionmentioning

confidence: 99%

Extremely Small-magnitude Accelerations Enhance Bone Regeneration: A Preliminary Study

Hwang

Lublinsky

Seo

et al. 2008

Clin Orthop Relat Res

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High-frequency, low-magnitude accelerations can be anabolic and anticatabolic to bone. We tested the hypothesis that application of these mechanical signals can accelerate bone regeneration in scaffolded and nonscaffolded calvarial defects. The cranium of experimental rats (n = 8) in which the 5-mm bilateral defects either contained a collagen scaffold or were left empty received oscillatory accelerations (45 Hz, 0.4 g) for 20 minutes per day for 3 weeks. Compared with scaffolded defects in the untreated control group (n = 6), defects with a scaffold and subject to oscillatory accelerations had a 265% greater fractional bone defect area 4 weeks after the surgery. After 8 weeks of healing (1-week recovery, 3 weeks of stimulation, 4 weeks without stimulation), the area (181%), volume (137%), and thickness (53%) of the regenerating tissue in the scaffolded defect were greater in experimental than in control animals. In unscaffolded defects, mechanical stimulation induced an 84% greater bone volume and a 33% greater thickness in the defect. These data provide preliminary evidence that extremely low-level, high-frequency accelerations can enhance osseous regenerative processes, particularly in the presence of a supporting scaffold.

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“…[1][2][3] It typically involves the culture of mesenchymal stem cells (MSCs), which are often grown on biomaterial scaffolds in an in vitro environment and in the presence of osteogenic growth factors and cell culture nutrients. However, these strategies have been associated with complications such as fibrous tissue encapsulation [4][5][6] and degradation of the tissue-engineered constructs when implanted in vivo.…”

mentioning

confidence: 99%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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In vitro bone regeneration strategies that prime mesenchymal stem cells (MSCs) with chondrogenic factors, to mimic aspects of the endochondral ossification process, have been shown to promote mineralization and vascularization by MSCs both in vitro and when implanted in vivo. However, these approaches required the use of osteogenic supplements, namely dexamethasone, ascorbic acid, and b-glycerophosphate, none of which are endogenous mediators of bone formation in vivo. Rather MSCs, endothelial progenitor cells, and chondrocytes all reside in proximity within the cartilage template and might paracrineally regulate osteogenic differentiation. Thus, this study tests the hypothesis that an in vitro bone regeneration approach that mimics the cellular niche existing during endochondral ossification, through coculture of MSCs, endothelial cells, and chondrocytes, will obviate the need for extraneous osteogenic supplements and provide an alternative strategy to elicit osteogenic differentiation of MSCs and mineral production. The specific objectives of this study were to (1) mimic the cellular niche existing during endochondral ossification and (2) investigate whether osteogenic differentiation could be induced without the use of any external growth factors. To test the hypothesis, we evaluated the mineralization and vessel formation potential of (a) a novel methodology involving both chondrogenic priming and the coculture of human umbilical vein endothelial cells (HUVECs) and MSCs compared with (b) chondrogenic priming of MSCs alone, (c) addition of HUVECs to chondrogenically primed MSC aggregates, (d-f) the same experimental groups cultured in the presence of osteogenic supplements and (g) a noncoculture group cultured in the presence of osteogenic growth factors alone. Biochemical (DNA, alkaline phosphatase [ALP], calcium, CD31 + , vascular endothelial growth factor [VEGF]), histological (alcian blue, alizarin red), and immunohistological (CD31 + ) analyses were conducted to investigate osteogenic differentiation and vascularization at various time points (1, 2, and 3 weeks). The coculture methodology enhanced both osteogenesis and vasculogenesis compared with osteogenic differentiation alone, whereas osteogenic supplements inhibited the osteogenesis and vascularization (ALP, calcium, and VEGF) induced through coculture alone. Taken together, these results suggest that chondrogenic and vascular priming can obviate the need for osteogenic supplements to induce osteogenesis of human MSCs in vitro, while allowing for the formation of rudimentary vessels.

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A tissue engineering approach to bone repair in large animal models and in clinical practice

Cited by 466 publications

References 100 publications

The rational use of animal models in the evaluation of novel bone regenerative therapies

The rational use of animal models in the evaluation of novel bone regenerative therapies

Extremely Small-magnitude Accelerations Enhance Bone Regeneration: A Preliminary Study

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

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