Name: adjustable stiffness, external fixator for the rat femur osteotomy and segmental bone defect models
Uploaded: 2014-10-09T13:00:00
Description: Watch this Scientific Journal Video about Adjustable Stiffness, External Fixator for the Rat Femur Osteotomy and Segmental Bone Defect Models at JoVE.com

This work was supported by the AO foundation (S-08-42G) and RISystem AG.
We would like to extend a very big &#34;thank you!&#34; to Stephan Zeiter&#39;s team at the AO Research Institute Davos, Switzerland for being so accommodating in allowing us to use their OR facilities for the filming of this surgical procedure.

Animal care and experimental protocols were followed in accordance with NIH guidelines and approved by the Beth Israel Deaconess Medical Center Institutional Animal Care and Use Committee, Boston, MA. (Protocol Number: 098-2009)
1. Preparation of Surgical Materials and Instruments
<ol>
	<li>Sterilize all surgical materials and instruments used to perform surgery prior to use. Pack needed materials, with or without an instrument tray, inside a folded cloth or wrapped paper and seal with autoc...

<ol>
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Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bone-healing+patterns+affected+by+loading,+fracture+fragment+stability,+fracture+type,+and+fracture+site+compression.">Bone-healing patterns affected by loading, fracture fragment stability, fracture type, and fracture site compression.</a> Clin Orthop Relat Res. , 8-17 (1993).</li><li>Augat, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Shear+movement+at+the+fracture+site+delays+healing+in+a+diaphyseal+fracture+model.">Shear movement at the fracture site delays healing in a diaphyseal fracture model.</a> J Orthop Res. 21, 1011-1017 (2003).</li><li>Augat, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+tissue+properties+in+bone+healing:+influence+of+size+and+stability+of+the+osteotomy+gap.">Local tissue properties in bone healing: influence of size and stability of the osteotomy gap.</a> J Orthop Res. 16, 475-481 (1998).</li><li>Claes, L., Augat, P., Suger, G., Wilke, H. 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N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interfragmentary+motion+in+tibial+osteotomies+stabilized+with+ring+fixators.">Interfragmentary motion in tibial osteotomies stabilized with ring fixators.</a> Clin Orthop Relat Res. , 163-172 (2002).</li><li>Goodship, A. E., Watkins, P. E., Rigby, H. S., Kenwright, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+fixator+frame+stiffness+in+the+control+of+fracture+healing.+An+experimental+study.">The role of fixator frame stiffness in the control of fracture healing. An experimental study.</a> J Biomech. 26, 1027-1035 (1993).</li><li>Williams, E. A., Rand, J. A., An, K. N., Chao, E. Y., Kelly, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+early+healing+of+tibial+osteotomies+stabilized+by+one-plane+or+two-plane+external+fixation.">The early healing of tibial osteotomies stabilized by one-plane or two-plane external fixation.</a> J Bone Joint Surg Am. 69, 355-365 (1987).</li><li>Wu, J. J., Shyr, H. S., Chao, E. Y., Kelly, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+osteotomy+healing+under+external+fixation+devices+with+different+stiffness+characteristics.">Comparison of osteotomy healing under external fixation devices with different stiffness characteristics.</a> J Bone Joint Surg Am. 66, 1258-1264 (1984).</li><li>Harrison, L. J., Cunningham, J. L., Stromberg, L., Goodship, A. 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Res. , 245-250 (2004).</li><li>Mark, H., Rydevik, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Torsional+stiffness+in+healing+fractures:+influence+of+ossification:+an+experimental+study+in+rats.">Torsional stiffness in healing fractures: influence of ossification: an experimental study in rats.</a> Acta Orthop. 76, 428-433 (2005).</li><li>McCann, R. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+osteoporosis+on+bone+mineral+density+and+fracture+repair+in+a+rat+femoral+fracture+model.">Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model.</a> J Orthop Res. 26, 384-393 (2008).</li><li>Betz, O. 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The most critical steps of a surgical procedure to create a large bone defect are: 1) choosing the appropriate body weight of the rat to match the size of the external fixator; 2) maintaining a sterile environment during the procedure; and 3) following the surgical procedure protocol.
The main goals of this study were to design, manufacture and characterize a new, variable stiffness external fixator for the rat femoral large defect model, and to use this fixator in determining the interplay be...

A number of studies have improved our understanding of the biologic mechanisms involved in bone tissue repair1-6. The effects of mechanical conditions on bone repair such as axial, shear and interfragmentary movements (IFMs) have been studied extensively7-15. In the past several years, more and more studies started to emerge describing the influence of mechanical environment on bone healing using fracture, osteotomy and large segmental bone defect in vivo models. Therefore, reliable fixation methods are needed to get reproducible and reliable study outcomes.
The mechanical environment around the healing fracture is very important as it determines the way the fracture will heal. Thus, the choice of fixation device is very important and should be carefully selected depending on the study design, and other factors such as gap size and the type of fracture. The fixation device&#8217;s mechanical properties are even more important when studying the bony healing of large bone defects to establish a fixation that provides not only a constant gap size throughout the experiment period of full weight bearing, but also an ideal mechanical environment for the healing bone. External fixators are commonly used in fracture and large bone defect experimental healing models because they have an advantage over other fixation devices. The main advantage of external fixators are that they allow for the change of the mechanical environment at the defect site in vivo without a secondary intervention, which can be achieved by changing or adjusting the stability bar of the device during the course of the experiment as the bone healing progresses. Moreover, it permits the application of specific local mechanical stimulation to enhance the repair of bone, and also provides the potential to measure the stiffness of callus tissue in vivo. Nevertheless, the devices also have a few disadvantages that include: irritation of soft tissue, infections and pin breakage.
Unfortunately, such implants were not available &#8220;off the shelf&#8221; at the time of the implant development, and investigators were forced to custom design their own fixators for an intended use. Therefore, one constraint of research in this area was the lack of experimental control over the local mechanical environment within a large segmental defect as well as osteotomies as it heals. The mechanical characteristics of an external fixator are defined by, and can be modulated by, a large number of variables which include: the distance between the pins, pin diameter, pin material, the number of pins, fixator bar length, fixator bar number, fixator bar material, fixator bar thickness and the distance from the bone surface to the fixator bar (offset). Surprisingly, only a paucity of studies could be found that have investigated the mechanical contributions of the individual components of fixators or whole frame configurations used in rodent studies16,18,28. For example, one study&#8217;s results showed that one of the main contributing factors in determining the total stiffness of the fixation construct was dominated by the flexibility of the pins in relation to their offset, diameter and material properties28. The results from the aforementioned studies clearly suggest that knowing the mechanical environment provided by the fixation device is extremely important, and yet, in many cases is not investigated in detail. The present paper reports the design, specifications, and in vivo implantation of an external fixator that addresses this issue. This fixator also allows for the modulation of the mechanical environment as healing progresses, a property that enables the study of the mechano-sensitivity of different stages of the healing process in vivo. Additionally, as well as imposing a controlled and reproducible local mechanical environment, its accessibility also allows for the modulation of this environment at different stages of bone healing.
The fixator we designed was based upon external fixation, which is widely used for fracture fixation16-21 and large defect models in experimental animals22-27. The difference between our external fixator and the other existing designs reported in the literature is that their stability bar is secured with screws to have a tight grip with Kirschner wires (K-wires). This type of design requires screws to be retightened biweekly (sometimes even weekly) to make sure that the distance of the offset is maintained as the loading is applied through weight bearing to prevent the loosening of the stability bar. If such loosening occurs, it allows for unwanted additional loading conditions such as angular, transverse and torsional shear movements to the healing bone (based on personal experience, communication with researchers). Knowing this, an external fixator was designed as such that when the stiffness of the fixator needs to be changed, it would be achieved by removing connection elements attached to the main module where the mounting pins are imbedded. The in vivo pilot experiment was performed with the new external fixator prototype to make sure that it meets all proposed demands before it is manufactured in larger quantities.
The main aim for this paper is to present a new surgical method for an external fixator used for large bone defects and osteotomies in the rat with the ability to change stiffness in vivo during the healing process. This fixation method is applied in vivo on the femora of rats.

<table border="0" cellpadding="0" cellspacing="0" width="848">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:232px;">Name of Material/ Equipment</td>
			<td style="width:283px;">Company</td>
			<td style="width:117px;">Catalog Number</td>
			<td style="width:216px;">Comments/Description</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">RatExFix simple 100%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.120</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">RatExFix simple 70%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.123</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">RatExFix simple 40%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.121</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">RatExFix simple 10%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.122</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:232px;">RatExFix Connection element 100%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.130</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">RatExFix Connection element 70%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.131</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">RatExFix Connection element 40%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.132</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">RatExFix Connection element 10%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.133</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">RatExFix Main body</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.611.101</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">RatExFix InterlockingScrew</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.412.110</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">RatExFix Mounting pin 0.85 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.412.100</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">RatExFix Saw Guide 100% 5 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.312.100</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Accu Pen 6V+</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.390.211</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">HandDrill</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.390.130</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Drill Bit 0.79 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.593.203</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Gigly wire saw 0.22 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.590.100</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Square box wrench 0.70 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.590.112</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Square box wrench 0.50 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.590.111</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Centering bit 1.00 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.592.205</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Scalpel Blade handle</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Scalpel Blade (Size 15)</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Tissue Forceps</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Scissors</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Retractor</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Needle Holder</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Henahan Elevator</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:232px;">S-shape curved dissecting and ligature forceps&#160;</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td>2</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Dressing Forceps</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td>2</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Sterile Fenestrated drape</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>for surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile gauze</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>for surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">5 ml syringe&#160;</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>&#160;for irrigation of defect</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">24-27G needle&#160;</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>&#160;for irrigation of defect</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">1cc Insulin syringes&#160;</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>for drug injections</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">sterile saline&#160;</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>for bone defect irrigation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">sterile gloves</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>to perform surgeries</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">chlorohezadine</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>disinfecting solution for surgical site</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Vicryl suture 4-0 with SH-1</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>to suture muscle&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Ethibond suture 3-0&#160;</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>to suture skin</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Isofluorine</td>
			<td style="width:283px;">Sigma-Aldrich</td>
			<td style="width:117px;"></td>
			<td>for anesthesia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Buprenorphine</td>
			<td style="width:283px;">Sigma-Aldrich</td>
			<td style="width:117px;"></td>
			<td>analgesia during and after the surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Cefazolin</td>
			<td style="width:283px;">Sigma-Aldrich</td>
			<td style="width:117px;"></td>
			<td>antibiotic during and after the surgery&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sprague-Dawley Rats or any other strain</td>
			<td>Charles River Laboratories International, Inc. (Wilmington, MA USA)&#160;</td>
			<td style="width:117px;"></td>
			<td></td>
		</tr>
	</tbody>
</table>

adjustable stiffness, external fixator for the rat femur osteotomy and segmental bone defect models

The mechanical environment around the healing of broken bone is very important as it determines the way the fracture will heal. Over the past decade there has been great clinical interest in improving bone healing by altering the mechanical environment through the fixation stability around the lesion. One constraint of preclinical animal research in this area is the lack of experimental control over the local mechanical environment within a large segmental defect as well as osteotomies as they heal. In this paper we report on the design and use of an external fixator to study the healing of large segmental bone defects or osteotomies. This device not only allows for controlled axial stiffness on the bone lesion as it heals, but it also enables the change of stiffness during the healing process in vivo. The conducted experiments have shown that the fixators were able to maintain a 5 mm femoral defect gap in rats in vivo during unrestricted cage activity for at least 8 weeks. Likewise, we observed no distortion or infections, including pin infections during the entire healing period. These results demonstrate that our newly developed external fixator was able to achieve reproducible and standardized stabilization, and the alteration of the mechanical environment of in vivo rat large bone defects and various size osteotomies. This confirms that the external fixation device is well suited for preclinical research investigations using a rat model in the field of bone regeneration and repair.

Design specifications
Stabilization of the rat femur with the external fixation system enables the creation of osteotomies from 0.5 to 5 mm. The external fixator system is a locked external fixator made of polyether ether ketone (PEEK - [the main body]) and titanium-aluminium-niobium alloy (TAN - [the mounting pins]), which offers a simple, reproducible and adjustable design, and is available in four different stiffnesses: 10, 40, 70 and 100% (100% being the standard, most rigid fixator (...

Watch this Scientific Journal Video about Adjustable Stiffness, External Fixator for the Rat Femur Osteotomy and Segmental Bone Defect Models at JoVE.com

Adjustable Stiffness, External Fixator for the Rat Femur Osteotomy and Segmental Bone Defect Models (Video) | JoVE

One constraint of preclinical research in the field of bone repair is the lack of experimental control over the local mechanical environment within a healing bone lesion. We report the design and use of an external fixator for bone repair with the ability to change fixator stiffness in vivo.

Adjustable Stiffness, External Fixator for the Rat Femur Osteotomy and Segmental Bone Defect Models

The mechanical environment around the healing of broken bone is very important as it determines the way the fracture will heal. Over the past decade there ...

Research

JoVE Journal

Medicine

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