Micro-computed tomography prediction of biomechanical strength in murine structural bone grafts

Reynolds, David G.; Hock, Colleen; Shaikh, Saad; Jacobson, Justin A.; Zhang, Xinping; Rubery, Paul T.; Beck, Christopher A.; O’Keefe, Regis J.; Lerner, Amy L.; Schwarz, Edward M.; Awad, Hani A.

doi:10.1016/j.jbiomech.2007.04.004

Cited by 53 publications

(76 citation statements)

References 36 publications

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“…A clinical study showed that the volume of bone formation is related to the number of progenitor cells that were transplanted for the treatment of human fracture nonunion (9). Moreover, another recent study, using the same murine bone graft model, demonstrated statistically significant correlations between the graft and callus volume and the ultimate torque and torsional rigidity of the site of bone repair (37). Taken together, the results from the present study indicate that the SDF-1/CXCR4 axis plays a key role in the recruitment of MSCs to sites of bone healing and promotes successful endochondral bone regeneration.…”

Section: Discussionmentioning

confidence: 99%

Stromal cell–derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model

Kitaori¹,

Ito²,

Schwarz³

et al. 2009

Arthritis & Rheumatism

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505

443

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Objective. Stromal cell-derived factor 1 (SDF-1; CXCL12/pre-B cell growth-stimulating factor) is a dominant chemokine in bone marrow and is known to be involved in inflammatory diseases, including rheumatoid arthritis. However, its role in bone repair remains unknown. The purpose of this study was to investigate the role of SDF-1 and its receptor, CXCR4, in bone healing.Methods. The expression of SDF-1 during the repair of a murine structural femoral bone graft was examined by real-time polymerase chain reaction and immunohistochemical analysis. The bone graft model was treated with anti-SDF-1 neutralizing antibody or TF14016, an antagonist for CXCR4, and evaluated by histomorphometry. The functional effect of SDF-1 on primary mesenchymal stem cells was determined by in vitro and in vivo migration assays. New bone formation in an exchanging-graft model was compared with that in the autograft models, using mice partially lacking SDF-1 (SDF-1 ؉/؊ ) or CXCR4 (CXCR4 ؉/؊ ).Results. The expression of SDF1 messenger RNA was increased during the healing of live bone grafts but was not increased in dead grafts. High expression of SDF-1 protein was observed in the periosteum of the live graft. New bone formation was inhibited by the administration of anti-SDF-1 antibody or TF14016. SDF-1 increased mesenchymal stem cell chemotaxis in vitro in a dose-dependent manner. The in vivo migration study demonstrated that mesenchymal stem cells recruited by SDF-1 participate in endochondral bone repair. Bone formation was decreased in SDF-1 ؉/؊ and CXCR4 ؉/؊ mice and was restored by the graft bones from CXCR4 ؉/؊ mice transplanted into the SDF-1 ؉/؊ femur, but not vice versa.Conclusion. SDF-1 is induced in the periosteum of injured bone and promotes endochondral bone repair by recruiting mesenchymal stem cells to the site of injury.

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Section: Discussionmentioning

confidence: 99%

Stromal cell–derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model

Kitaori¹,

Ito²,

Schwarz³

et al. 2009

Arthritis & Rheumatism

Self Cite

505

443

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“…We performed destructive torsional testing of the allografted and unoperated contralateral femurs to determine torsional rigidity and failure torque as we previously described [17,20] using a materials testing machine (MTS Systems Corp, Eden Prairie, MN, USA). Two additional unoperated canine femurs from a dog of the same breed and approximate weight that was not part of the in vivo study were included as controls.…”

Section: Methodsmentioning

confidence: 99%

Quantifying Massive Allograft Healing of the Canine Femur In Vivo and Ex Vivo: A Pilot Study

Santoni

Ehrhart

Betancourt-Benitez

et al. 2012

Clinical Orthopaedics &Amp; Related Research

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Background Allograft integration in segmental osseous defects is unpredictable. Imaging techniques have not been applied to investigate angiogenesis and bone formation during allograft healing in a large-animal model. Questions/purposes We used dynamic contrast-enhanced (DCE)-MRI and cone beam (CB)-CT to quantify vascularity and bone volume in a canine femoral allograft model and determined their relationship with biomechanical testing and histomorphometry. Methods Femoral ostectomy was performed in three dogs and reconstructed with a 5-cm allograft and compression plate. At 0.5, 3, and 6 months, we performed DCE-MRI to quantify vascular permeability (Ktrans) and perfused fraction and CB-CT to quantify bone volume. We also performed posteuthanasia torsional testing and dynamic histomorphometry of the grafted and nonoperated femurs. Results DCE-MRI confirmed the avascular nature of allograft healing (perfused fraction, 2.08%-3.25%). CB-CT demonstrated new bone formation at 3 months (26.2, 3.7, and 2.2 cm 3

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“…An analysis of the connectivity of the graft to the host bones indicates that allografts are largely disconnected from the host especially at 6 weeks. From these studies, we identified three predictive correlations between combinations of the micro-CT parameters and the measured ultimate torque and torsional rigidity of the murine grafts, respectively [75,98]: (1) amount of new bone formation around bone graft; (2) cross-sectional polar moment of inertia of the graft callus; and (3) connectivity of the bone allograft to the host bone.…”

Section: Design Rationale and Outcome Evaluations For Tissue-engineermentioning

confidence: 99%

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

Zhang

Awad

O’Keefe

et al. 2008

Clin Orthop Relat Res

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Autograft is superior to both allograft and synthetic bone graft in repair of large structural bone defect largely due to the presence of multipotent mesenchymal stem cells in periosteum. Recent studies have provided further evidence that activation, expansion and differentiation of the donor periosteal progenitor cells are essential for the initiation of osteogenesis and angiogenesis of donor bone graft healing. The formation of donor cell-derived periosteal callus enables efficient host-dependent graft repair and remodeling at the later stage of healing. Removal of periosteum from bone autograft markedly impairs healing whereas engraftment of multipotent mesenchymal stem cells on bone allograft improves healing and graft incorporation. These studies provide rationale for fabrication of a biomimetic periosteum substitute that could fit bone of any size and shape for enhanced allograft healing and repair. The success of such an approach will depend on further understanding of the molecular signals that control inflammation, cellular recruitment as well as mesenchymal stem cell differentiation and expansion during the early phase of the repair process. It will also depend on multidisciplinary collaborations between biologists, material scientists and bioengineers to address issues of material selection and modification, biological and biomechanical parameters for functional evaluation of bone allograft healing.

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Micro-computed tomography prediction of biomechanical strength in murine structural bone grafts

Cited by 53 publications

References 36 publications

Stromal cell–derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model

Stromal cell–derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model

Quantifying Massive Allograft Healing of the Canine Femur In Vivo and Ex Vivo: A Pilot Study

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

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