Structural and biomechanical responses of osseous healing: A novel murine nonunion model

被引：10

作者：

Chaubey A. ^{[1
,6
]}

Grawe B. ^{[2
]}

Meganck J.A. ^{[5
]}

Dyment N. ^{[1
]}

Inzana J. ^{[3
]}

Jiang X. ^{[4
]}

Connolley C. ^{[2
]}

Awad H. ^{[3
]}

Rowe D. ^{[4
]}

Kenter K. ^{[2
]}

Goldstein S.A. ^{[5
]}

Butler D. ^{[1
]}

机构：

[1] Biomedical Engineering Program, School of Energy, Environmental and Biological and Medical Engineering, University of Cincinnati, Cincinnati, OH 45221-0048

[2] Department of Orthopaedic Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH

[3] Department of Biomedical Engineering, School of Medicine and Dentistry, University of Rochester, Rochester, NY

[4] Center of Regenerative Medicine and Skeletal Development, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT

[5] Department of Orthopaedic Surgery, School of Medicine, University of Michigan, Ann Arbor, MI

[6] Mazumdar Shaw Center for Translational Research, Bangalore 560099, Karnataka

来源：

Journal of Orthopaedics and Traumatology | 2013年 / 14卷 / 4期

基金：

美国国家卫生研究院;

关键词：

Bone; Critical defect; Fracture; Healing; Nonunion;

D O I：

10.1007/s10195-013-0269-4

中图分类号：

学科分类号：

摘要：

Background: Understanding the biological mechanisms of why certain fractures are at risk for delayed healing or nonunion requires translational animal models that take advantage of transgenic and other genetic manipulation technologies. Reliable murine nonunion models can be an important tool to understand the biology of nonunion. In this study, we report the results of a recently established model for creating critical defects that lead to atrophic nonunions based on a unique fracture fixation technique. Materials and methods: Subcritical (0.6 mm long) and critical (1.6 mm long) defects were created in femurs of 10-week-old double transgenic (Col1/Col2) mice and stabilized using a custom-designed plate and four screws. Four groups were used: normal, sham, subcritical, and critical. Histology (n = 3 for each group) was analyzed at 2 and 5 weeks, and micro-computed tomography (μCT) and torsional biomechanics (n = 12 for each group) were analyzed at 5 weeks. Results: Subcritical defects showed healing at 2 weeks and were completely healed by 5 weeks, with biomechanical properties not significantly different from normal controls. However, critical defects showed no healing by histology or μCT. These nonunion fractures also displayed no torsional stiffness or strength in 10 of 12 cases. Conclusions: Our murine fracture model creates reproducible and reliable nonunions and can serve as an ideal platform for studying molecular pathways to contrast healing versus nonhealing events and for evaluating innovative therapeutic approaches to promote healing of a challenging osseous injury. © 2012 The Author(s).

引用

页码：247 / 257

页数：10

共 13 条

[1]

Choi P., Ogilvie C., Thompson Z., Et al., Cellular and molecular characterization of a murine non-union model, J Orthop Res, 22, pp. 1100-1107, (2004)

[2]

Kwong F.N., Harris M.B., Recent developments in the biology of fracture repair, J Am Acad Orthop Surg, 16, pp. 619-625, (2008)

[3]

Kurtz S.M., Ong K.L., Schmier J., Et al., Future clinical and economic impact of revision total hip and knee arthroplasty, J Bone Joint Surg Am, 89, SUPPL. 3, pp. 144-151, (2007)

[4]

Choi P., Ogilvie C., Thompson Z., Et al., Cellular and molecular characterization of a murine non-union model, J Orthop Res, 22, pp. 1100-1107, (2004)

[5]

Harrison L.J., Cunningham J.L., Stromberg L., Goodship A.E., Controlled induction of a pseudarthrosis: A study using a rodent model, J Orthop Trauma, 17, pp. 11-21, (2003)

[6]

Hietaniemi K., Peltonen J., Paavolainen P., An experimental model for non-union in rats, Injury, 26, pp. 681-686, (1995)

[7]

Oetgen M.E., Merrell G.A., Troiano N.W., Et al., Development of a femoral non-union model in the mouse, Injury, 39, pp. 1119-1126, (2008)

[8]

Holstein J.H., Garcia P., Histing T., Et al., Advances in the establishment of defined mouse models for the study of fracture healing and bone regeneration, J Orthop Trauma, 23, (2009)

[9]

Chokalingam K., Juncosa-Melvin N., Hunter S.A., Et al., Tensile stimulation of murine stem cell-collagen sponge constructs increases collagen type I gene expression and linear stiffness, Tissue Eng Part A, 15, pp. 2561-2570, (2009)

[10]

Garcia P., Holstein J.H., Maier S., Et al., Development of a reliable non-union model in mice, J Surg Res, 147, pp. 84-91, (2008)

← 1 2 →