- Email: [email protected]
An Innovative Intramedullary Nail for Stabilizing Mouse Femoral Defects
Journal of Surgical Research 167, 39–40 (2011) doi:10.1016/j.jss.2010.05.062
COMMENTARY An Innovative Intramedullary Nail for Stabilizing Mouse Femoral Defects Submitted for publication April 28, 2010
The study by Garcia and colleagues, published in the Journal of Surgical Research, describes an innovative intramedullary fixator for stabilizing long bone defects in mice [1]. The authors demonstrate that their device, which they have named the Locking Mouse Nail, can stabilize mouse femoral segmental defects measuring 0, 0.25, and 2.0 mm in length. Furthermore, by showing that 0.25 mm gaps show complete healing while 2 mm gaps develop atrophic non-unions, the authors have helped confirm that critical-size femoral defects in mice are 2 mm or less in length [2]. Generally speaking, critical-sized bone defect models are distinguished from fracture healing models by their behavior following rigid fixation [2–5]. While fracture models are expected to universally achieve bone healing, segmental defect models involving a substantial gap achieve a fibrous union. Fracture models can be used to describe the cellular events surrounding normal bone healing, while segmental defect models are useful for understanding the limitations of those cellular events, as well as providing a platform for evaluating methodologies for treating the non-unions. The challenge to date has been the development of effective fixation systems for the mouse, which reproduce the types of hardware that are commonly used clinically. In this study, the authors have combined an intramedullary rod with transcortical pins to achieve multi-dimensional stabilization of individual bone segments. The rod prevents angular deformity across the fracture, while the pins prevent axial and rotational movements. They evaluated the construct’s stability, and found it is exceeded only by an external fixation system. As the authors point out, the chief advantage of this system is that it allows the study of bone healing in transgenic and knockout mouse models. For instance, the role in osteoblast function of a variety signaling pathways, such as the Wnts, as well as the efficacy of novel agents which modulate these pathways, can now be evaluated during fracture healing [6–10]. Likewise, the role of stem cells and other osteoprogenitor cells during the formation of new bone can be better defined [11]. The greatest limitations that the model offers may be availability, cost, and ease of use. It is as yet unclear whether this device will be available for widespread dissemination, and how much training an investigator will need before employing it consistently. Despite these concerns, the authors have done innovative work in creating novel mouse fixation models. They should be commended and
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0022-4804/$36.00 Ó 2011 Elsevier Inc. All rights reserved.
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JOURNAL OF SURGICAL RESEARCH: VOL. 167, NO. 1, MAY 1, 2011
encouraged to use the device to begin answering basic questions about fracture healing. Mahesh H. Mankani, M.D. Department of Surgery University of California, San Francisco 1001 Potrero Avenue, Box 0807 San Francisco, CA 94143-0807 E-mail: [email protected].
REFERENCES 1. Garcia P, Herwerth S, Matthys R, et al. The LockingMouseNail-A new implant for standardized stable osteosynthesis in mice. J Surg Res 2010, in press. 2. Garcia P, Holstein JH, Maier S, et al. Development of a reliable non-union model in mice. J Surg Res 2008;147:84. Epub 2007 Oct 29. 3. Holstein JH, 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 2009; 23:S31. 4. Garcia P, Holstein JH, Histing T, et al. A new technique for internal fixation of femoral fractures in mice: Impact of stability on fracture healing. J Biomech 2008;41:1689. Epub 2008 May 6. 5. Reichert JC, Saifzadeh S, Wullschleger ME, et al. The challenge of establishing preclinical models for segmental bone defect research. Biomaterials 2009;30:2149. Epub 2009 Feb 10. 6. Secreto FJ, Hoeppner LH, Westendorf JJ. Wnt signaling during fracture repair. Curr Osteoporos Rep 2009;7:64. 7. Canalis E. New treatment modalities in osteoporosis. Endocr Pract 2010;29:1. 8. Deal C. Potential new drug targets for osteoporosis. Nat Clin Pract Rheumatol 2009;5:20. 9. Komatsu DE, Mary MN, Schroeder RJ, et al. Modulation of Wnt signaling influences fracture repair. J Orthop Res 2010;28:928. 10. Komatsu DE, Warden SJ. The control of fracture healing and its therapeutic targeting: Improving upon nature. J Cell Biochem 2010;109:302. 11. Krause U, Harris S, Green A, et al. Pharmaceutical modulation of canonical Wnt signaling in multipotent stromal cells for improved osteoinductive therapy. Proc 107:4147– 4152. Epub 2010 Feb 11.
COMMENTARY An Innovative Intramedullary Nail for Stabilizing Mouse Femoral Defects Submitted for publication April 28, 2010
The study by Garcia and colleagues, published in the Journal of Surgical Research, describes an innovative intramedullary fixator for stabilizing long bone defects in mice [1]. The authors demonstrate that their device, which they have named the Locking Mouse Nail, can stabilize mouse femoral segmental defects measuring 0, 0.25, and 2.0 mm in length. Furthermore, by showing that 0.25 mm gaps show complete healing while 2 mm gaps develop atrophic non-unions, the authors have helped confirm that critical-size femoral defects in mice are 2 mm or less in length [2]. Generally speaking, critical-sized bone defect models are distinguished from fracture healing models by their behavior following rigid fixation [2–5]. While fracture models are expected to universally achieve bone healing, segmental defect models involving a substantial gap achieve a fibrous union. Fracture models can be used to describe the cellular events surrounding normal bone healing, while segmental defect models are useful for understanding the limitations of those cellular events, as well as providing a platform for evaluating methodologies for treating the non-unions. The challenge to date has been the development of effective fixation systems for the mouse, which reproduce the types of hardware that are commonly used clinically. In this study, the authors have combined an intramedullary rod with transcortical pins to achieve multi-dimensional stabilization of individual bone segments. The rod prevents angular deformity across the fracture, while the pins prevent axial and rotational movements. They evaluated the construct’s stability, and found it is exceeded only by an external fixation system. As the authors point out, the chief advantage of this system is that it allows the study of bone healing in transgenic and knockout mouse models. For instance, the role in osteoblast function of a variety signaling pathways, such as the Wnts, as well as the efficacy of novel agents which modulate these pathways, can now be evaluated during fracture healing [6–10]. Likewise, the role of stem cells and other osteoprogenitor cells during the formation of new bone can be better defined [11]. The greatest limitations that the model offers may be availability, cost, and ease of use. It is as yet unclear whether this device will be available for widespread dissemination, and how much training an investigator will need before employing it consistently. Despite these concerns, the authors have done innovative work in creating novel mouse fixation models. They should be commended and
39
0022-4804/$36.00 Ó 2011 Elsevier Inc. All rights reserved.
40
JOURNAL OF SURGICAL RESEARCH: VOL. 167, NO. 1, MAY 1, 2011
encouraged to use the device to begin answering basic questions about fracture healing. Mahesh H. Mankani, M.D. Department of Surgery University of California, San Francisco 1001 Potrero Avenue, Box 0807 San Francisco, CA 94143-0807 E-mail: [email protected].
REFERENCES 1. Garcia P, Herwerth S, Matthys R, et al. The LockingMouseNail-A new implant for standardized stable osteosynthesis in mice. J Surg Res 2010, in press. 2. Garcia P, Holstein JH, Maier S, et al. Development of a reliable non-union model in mice. J Surg Res 2008;147:84. Epub 2007 Oct 29. 3. Holstein JH, 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 2009; 23:S31. 4. Garcia P, Holstein JH, Histing T, et al. A new technique for internal fixation of femoral fractures in mice: Impact of stability on fracture healing. J Biomech 2008;41:1689. Epub 2008 May 6. 5. Reichert JC, Saifzadeh S, Wullschleger ME, et al. The challenge of establishing preclinical models for segmental bone defect research. Biomaterials 2009;30:2149. Epub 2009 Feb 10. 6. Secreto FJ, Hoeppner LH, Westendorf JJ. Wnt signaling during fracture repair. Curr Osteoporos Rep 2009;7:64. 7. Canalis E. New treatment modalities in osteoporosis. Endocr Pract 2010;29:1. 8. Deal C. Potential new drug targets for osteoporosis. Nat Clin Pract Rheumatol 2009;5:20. 9. Komatsu DE, Mary MN, Schroeder RJ, et al. Modulation of Wnt signaling influences fracture repair. J Orthop Res 2010;28:928. 10. Komatsu DE, Warden SJ. The control of fracture healing and its therapeutic targeting: Improving upon nature. J Cell Biochem 2010;109:302. 11. Krause U, Harris S, Green A, et al. Pharmaceutical modulation of canonical Wnt signaling in multipotent stromal cells for improved osteoinductive therapy. Proc 107:4147– 4152. Epub 2010 Feb 11.