この出版物で報告された研究は、国立研究所の関節炎、筋骨格系に支えられて、賞の下で健康の国民の協会の皮膚疾患番号 F30AR071201 と R01AR066028。

<ol>
	<li>Corso, P., Finkelstein, E., Miller, T., Fiebelkorn, I., Zaloshnja, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incidence+and+lifetime+costs+of+injuries+in+the+United+States.">Incidence and lifetime costs of injuries in the United States.</a> Injury Prevention. 12 (4), 212-218 (2006).</li><li>Nguyen, N. D., Ahlborg, H. G., Center, J. R., Eisman, J. A., Nguyen, T. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Residual+lifetime+risk+of+fractures+in+women+and+men.">Residual lifetime risk of fractures in women and men.</a> Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research. 22 (6), 781-788 (2007).</li><li>Thompson, Z., Miclau, T., Hu, D., Helms, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+model+for+intramembranous+ossification+during+fracture+healing.">A model for intramembranous ossification during fracture healing.</a> Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society. 20 (5), 1091-1098 (2002).</li><li>Cheung, K. M. C., Kaluarachi, K., Andrew, G., Lu, W., Chan, D., Cheah, K. S. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+externally+fixed+femoral+fracture+model+for+mice.">An externally fixed femoral fracture model for mice.</a> Journal of Orthopaedic Research. 21 (4), 685-690 (2003).</li><li>Connolly, C. K., 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=A+reliable+externally+fixated+murine+femoral+fracture+model+that+accounts+for+variation+in+movement+between+animals.">A reliable externally fixated murine femoral fracture model that accounts for variation in movement between animals.</a> Journal of Orthopaedic Research. 21 (5), 843-849 (2003).</li><li>Histing, T., 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=An+internal+locking+plate+to+study+intramembranous+bone+healing+in+a+mouse+femur+fracture+model.">An internal locking plate to study intramembranous bone healing in a mouse femur fracture model.</a> Journal of Orthopaedic Research. 28 (3), 397-402 (2010).</li><li>Gr&#246;ngr&#246;ft, I., 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=Fixation+compliance+in+a+mouse+osteotomy+model+induces+two+different+processes+of+bone+healing+but+does+not+lead+to+delayed+union.">Fixation compliance in a mouse osteotomy model induces two different processes of bone healing but does not lead to delayed union.</a> Journal of Biomechanics. 42 (13), 2089-2096 (2009).</li><li>Bonnarens, F., Einhorn, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Production+of+a+standard+closed+fracture+in+laboratory+animal+bone.">Production of a standard closed fracture in laboratory animal bone.</a> Journal of Orthopaedic Research. 2 (1), 97-101 (1984).</li><li>Huang, C., 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=The+spatiotemporal+role+of+COX-2+in+osteogenic+and+chondrogenic+differentiation+of+periosteum-derived+mesenchymal+progenitors+in+fracture+repair.">The spatiotemporal role of COX-2 in osteogenic and chondrogenic differentiation of periosteum-derived mesenchymal progenitors in fracture repair.</a> PloS One. 9 (7), 100079 (2014).</li><li>Waki, T., 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=Profiling+microRNA+expression+during+fracture+healing.">Profiling microRNA expression during fracture healing.</a> BMC Musculoskeletal Disorders. 17, 83 (2016).</li><li>Yee, C. S., 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=Sclerostin+antibody+treatment+improves+fracture+outcomes+in+a+Type+I+diabetic+mouse.">Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse.</a> Bone. 82, 122-134 (2016).</li><li>Wong, E., 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=A+novel+low-molecular-weight+compound+enhances+ectopic+bone+formation+and+fracture+repair.">A novel low-molecular-weight compound enhances ectopic bone formation and fracture repair.</a> The Journal of Bone and Joint Surgery. American Volume. 95 (5), 454-461 (2013).</li><li>Prodinger, P. 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=Does+Anticoagulant+Medication+Alter+Fracture-Healing?+A+Morphological+and+Biomechanical+Evaluation+of+the+Possible+Effects+of+Rivaroxaban+and+Enoxaparin+Using+a+Rat+Closed+Fracture+Model.">Does Anticoagulant Medication Alter Fracture-Healing? A Morphological and Biomechanical Evaluation of the Possible Effects of Rivaroxaban and Enoxaparin Using a Rat Closed Fracture Model.</a> PloS One. 11 (7), 0159669 (2016).</li><li>Menzdorf, L., 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+pamidronate+influences+fracture+healing+in+a+rodent+femur+fracture+model:+an+experimental+study.">Local pamidronate influences fracture healing in a rodent femur fracture model: an experimental study.</a> BMC Musculoskeletal Disorders. 17, 255 (2016).</li><li>Hagiwara, Y., 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=Fixation+stability+dictates+the+differentiation+pathway+of+periosteal+progenitor+cells+in+fracture+repair.">Fixation stability dictates the differentiation pathway of periosteal progenitor cells in fracture repair.</a> Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society. 33 (7), 948-956 (2015).</li><li>Gardner, M. J., 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=Differential+fracture+healing+resulting+from+fixation+stiffness+variability:+a+mouse+model.">Differential fracture healing resulting from fixation stiffness variability: a mouse model.</a> Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association. 16 (3), 298-303 (2011).</li><li>Catma, M. F., 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=Remote+ischemic+preconditioning+enhances+fracture+healing.">Remote ischemic preconditioning enhances fracture healing.</a> Journal of Orthopaedics. 12 (4), 168-173 (2015).</li><li>Lichte, 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=Impaired+Fracture+Healing+after+Hemorrhagic+Shock.">Impaired Fracture Healing after Hemorrhagic Shock.</a> Mediators of Inflammation. 2015, 132451 (2015).</li><li>Lopas, L. A., 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=Fractures+in+geriatric+mice+show+decreased+callus+expansion+and+bone+volume.">Fractures in geriatric mice show decreased callus expansion and bone volume.</a> Clinical Orthopaedics and Related Research. 472 (11), 3523-3532 (2014).</li><li>Bonnarens, F., Einhorn, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Production+of+a+standard+closed+fracture+in+laboratory+animal+bone.">Production of a standard closed fracture in laboratory animal bone.</a> Journal of orthopaedic research. 2 (1), 97-101 (1984).</li><li>Marturano, J. E., 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=An+improved+murine+femur+fracture+device+for+bone+healing+studies.">An improved murine femur fracture device for bone healing studies.</a> Journal of Biomechanics. 41 (6), 1222-1228 (2008).</li><li>Jackson, R. W., Reed, C. A., Israel, J. A., Abou-Keer, F. K., Garside, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Production+of+a+standard+experimental+fracture.">Production of a standard experimental fracture.</a> Canadian Journal of Surgery. Journal Canadien De Chirurgie. 13 (4), 415-420 (1970).</li><li>Byrne, M., Cleveland, B., Marturano, J., Wixted, J., Billiar, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+of+a+reproducible+murine+femoral+fracture+device.+Conference:+Bioengineering+Conference,+2007.">Design of a reproducible murine femoral fracture device. Conference: Bioengineering Conference, 2007.</a> NEBC '07. IEEE 33rd Annual Northeast. , (2007).</li><li>Carter, D. R., Hayes, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Compact+bone+fatigue+damage-I.+Residual+strength+and+stiffness.">Compact bone fatigue damage-I. Residual strength and stiffness.</a> Journal of Biomechanics. 10 (5), 325-337 (1977).</li><li>McGee, A., Qureshi, A., Porter, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Review+of+the+biomechanics+and+patterns+of+limb+fractures.">Review of the biomechanics and patterns of limb fractures.</a> Trauma. 6 (1), 29-40 (2004).</li></ol>

著者が明らかに何もありません。

この破壊の最適化と世代のプロトコルは、破壊パラメーターに派生し、正確、再現性のある、横骨折を生成する低侵襲の手順を実行する効率的な方法を研究者を提供します。さらに、このプロトコルは、研究者の間の法の整合性を促進する破壊生成パラメーターの共通セットを確立します。これらのパラメーターは、さまざまなパラメーター (例えば年齢、性別、性別、および遺伝子?...

骨折治癒の研究大臨床と経済問題に対処する必要があります。毎年以上 1200 万骨折はアメリカ合衆国1, 原価計算 $ 800 億年2あたりで扱われます。男性または女性の苦しみの一生に破壊する可能性は 25%、44%、それぞれ3。骨折治癒に関連する問題は人口年齢として増加併存疾患とともに増加する期待されます。勉強してこの問題に対処するには、堅牢なモデル破壊発生と安定化が必要です。齧歯動物モデルは、この目的に最適です。彼らは臨床的に意味を提供し、アドレス特定の条件 (すなわち、複数けが、オープン、クローズ、虚血、感染骨折) を変更することができます。臨床シナリオの他、動物破壊モデルは骨の生物学の治療とデバイスの開発を理解することにとって重要です。しかし、介入の違いを勉強しよう矛盾破壊発生によって導入された変動によって複雑になる可能性があります。したがって、動物モデルでの再現性と一貫して閉じた割れ目を生成する筋骨格系の研究分野に不可欠です。
正しく適切な遺伝的背景、性別、年齢、および環境条件を確保することによって潜在的な主題の不均一性の制御、にもかかわらず臨床的に関連する一貫性のある骨の傷害の生産は重要な変数に影響を与える再現性であり、制御する必要があります。一貫性のない骨折を使用して統計の比較実験の騒音と高変動4; 悩まされていますさらに、破壊の可変性は、サンプル サイズや粉砕または挿骨折で安楽死する必要性を向上させる必要があるのため不必要な動物の死につながります。記載法の目的は、サンプル タイプに固有の破壊生成パラメーターを最適化することで、コンシス テント ・ フラクチャの場所とパターンをもたらします。
破壊発生の現在のモデルは、それぞれ独自の長所と短所を持つ 2 つの広範なカテゴリに分類されます。開放骨折 (骨切り術) モデルは、その後骨折が骨を切断または弱くなり、その後、手動でそれを壊す5,6,7,8によって誘導される骨を公開する手術を受けます。このメソッドの利点は、骨折部位とより一貫性のある破壊位置とパターンの直接可視化です。しかし、アプローチの生理学的および臨床関連性と損傷の発生メカニズムは、限定されます。また、外科的アプローチと汚染のリスクにさらされている齧歯動物で長時間の閉鎖破壊発生の open メソッドが必要です。
閉じた技術オープン技術の制限の多くに対処します。閉じた技術を骨折骨や周囲の組織は、人間の臨床的傷害で見られるそれらに類似の損傷を誘導する外部から鈍力外傷を使用して生成します。最も一般的な方法は、1984年9Bonnarens とアインによって記述されていた。彼らは、任意の外部の皮膚の傷を引き起こすことがなく、骨を破壊する鈍的外傷を与えるために使用されている加重ギロチンをについて説明します。このメソッドは、遺伝学10,11, 薬物療法12,13,14,15, 力学16,の効果を研究に広く採用されている17、生理18,19,20癒しのマウスおよびラットの骨。閉じたメソッドの利点は、生理学的に関連する骨折は、実験の再現性と厳しさが破壊の不均一性によって制限されます。一貫性のない破壊の発生は、限られたグループ間の差別化、失われた標本、統計的有意性を達成するために必要な動物の増加の結果します。
破壊発生と安定化の変動を制御することは、意味のある結果を生成する不可欠です。正しく破壊修理の生物学を勉強、するためにシンプルで確実な破壊のモデルが必要です。モデル変数マウスの遺伝的背景の齧歯動物種、骨型 (大腿骨または脛骨、たとえば) に翻訳する必要があります、突然変異を誘発しました。さらに、理想的な手順は技術的に単純な一貫性のある結果を生みます。アドレス破壊の不均一性に記載メソッドはパラメーターを最適化し、年齢、性別、および遺伝子型に関係なく一貫して閉じた割れ目を生成するために使用することができます制御された破壊装置の建設。

<table><tbody><tr><td>&lt;strong&gt;Support Subassembly&lt;/strong&gt;</td><td></td><td></td><td>Supplementary Figure 1</td></tr><tr><td>Beam, Support--Jaw Section&amp;nbsp;</td><td>80/20</td><td>1003 x 9.00</td><td>w/ #7042 at A, C, in Left End</td></tr><tr><td>Beam, Support--Horizontal Section</td><td>80/20</td><td>1002 x 14.00</td><td></td></tr><tr><td>Beam, Support--Vertical 1</td><td>80/20</td><td>1050 x 10.50&amp;nbsp;</td><td>w/ #7042 at A in Left End and at A in Right End</td></tr><tr><td>Beam, Support--Vertical 2</td><td>80/20</td><td>1010 x 10.50&amp;nbsp;</td><td>w/ #7042 at D, B in Left End and at A in Right End</td></tr><tr><td>Beam, Support--Plate Mount</td><td>80/20</td><td>1030 x 8.00&amp;nbsp;</td><td>w/ #7036 at Left End</td></tr><tr><td>Beam, Support--Magnet</td><td>80/20</td><td>1010 x 13.50&amp;nbsp;</td><td>w/ #7042 at A, C, in Right End</td></tr><tr><td>Anchors (3)</td><td>80/20</td><td>3392</td><td></td></tr><tr><td>Double Anchor (3)</td><td>80/20</td><td>3091</td><td></td></tr><tr><td>Bolt Assembly (6)</td><td>80/20</td><td>3386</td><td>1/4-20 x 3/8&quot;</td></tr><tr><td>Button Head Socket Cap Screw (6)</td><td>80/20</td><td>3604</td><td>1/4-20 x 3/4&quot;</td></tr><tr><td>&lt;strong&gt;Ram Subassembly&lt;/strong&gt;</td><td></td><td></td><td>Supplementary Figure 2</td></tr><tr><td>Block, Stop</td><td>Custom</td><td></td><td>Supplementary Figure 3</td></tr><tr><td>Block, Guide</td><td>Custom</td><td></td><td>Supplementary Figure 3</td></tr><tr><td>Rod, Ram</td><td>Custom</td><td></td><td>Supplementary Figure 4</td></tr><tr><td>Alignment Screw</td><td>Custom</td><td></td><td>Supplementary Figure 5</td></tr><tr><td>Plate, Mounting</td><td>Custom</td><td></td><td>Supplementary Figure 6</td></tr><tr><td>Linear Sleeve Bearing (2)</td><td>McMaster-Carr</td><td>8649T2</td><td></td></tr><tr><td>Hex Nut (3)</td><td>McMaster-Carr</td><td>92673A125</td><td>3/8-16 UNC</td></tr><tr><td>Socket Cap Screw (8)</td><td>McMaster-Carr</td><td>92196A108</td><td>4/40 x 3/8&quot;</td></tr><tr><td>Socket Cap Screw (6)</td><td>McMaster-Carr</td><td>92196A032</td><td>4/40 x 1 1/8&quot;</td></tr><tr><td>Socket Cap Screw (1)</td><td>McMaster-Carr</td><td>92196A267&amp;nbsp;</td><td>10/32 3/8&quot;</td></tr><tr><td>&lt;strong&gt;Magnet Subassembly&lt;/strong&gt;</td><td></td><td></td><td>Supplementary Figure 7</td></tr><tr><td>Mount, Magnet</td><td>Custom</td><td></td><td>Supplementary Figure 8</td></tr><tr><td>Power Supply</td><td>McMaster-Carr</td><td>70235K23</td><td></td></tr><tr><td>Foot Switch</td><td>McMaster-Carr</td><td>7376k2</td><td></td></tr><tr><td>Electromagnet</td><td>McMaster-Carr</td><td>5698k111</td><td></td></tr><tr><td>Wire - 10 feet</td><td>McMaster-Carr</td><td>9936k12</td><td></td></tr><tr><td>Rod, Magnet</td><td>McMaster-Carr</td><td>95412A566</td><td>1/4&quot; Threaded Rod x 7&quot;</td></tr><tr><td>Corner Bracket (6)</td><td>80/20</td><td>4108</td><td></td></tr><tr><td>Socket Cap Screw (1)</td><td>McMaster-Carr</td><td>92196A705</td><td>10/32 1 1/4&quot;</td></tr><tr><td>Hex Nut (4)</td><td>McMaster-Carr</td><td>92673A113</td><td>1/4-20 UNC</td></tr><tr><td>&lt;strong&gt;Complete Assembly&lt;/strong&gt;</td><td></td><td></td><td>Supplementary Figure 9</td></tr><tr><td>Bracket, Leg Jaw (2)</td><td>Custom</td><td></td><td>Supplementary Figure 10</td></tr><tr><td>Platform, Fracture</td><td>Custom</td><td></td><td>Supplementary Figure 11</td></tr><tr><td>Jig, Positioning-Fracture</td><td>Custom</td><td></td><td>Supplementary Figure 12</td></tr><tr><td>&lt;strong&gt;Other&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Pin Cutter</td><td>Medical Supplies and Equipment</td><td>150S</td><td></td></tr><tr><td>Needles</td><td>Sigma</td><td>Z192430, Z192376&amp;nbsp;</td><td>23g x 1.5&quot; - mouse femur, 27g x 1.25&quot; - mouse tibia</td></tr></tbody></table>

fracture apparatus design and protocol optimization for closed-stabilized fractures in rodents

動物モデルにおける一貫性のある安定した骨折の信頼性の高い世代は、骨再生の生物学を理解し、治療とデバイス開発に不可欠です。ただし、利用可能な傷害モデルは無駄な動物とリソースや不完全なデータの不整合が悩まされています。この破壊の不均一性の問題に対処するため記載法の目的は、それぞれの動物に固有の破壊生成パラメーターを最適化し、コンシス テント ・ フラクチャの場所とパターンを生成します。このプロトコルは、ボーンのサイズとマウス系統間に存在可能性があります、ラットなど他の種でコンシス テント ・ フラクチャを生成する合わせることができる形態の変化を占めています。さらに、コスト効率の高い、調節可能な破壊装置を説明します。現在の安定した破砕技術と比較して、最適化のプロトコルと新しい破壊装置安定破壊パターンと位置整合性の向上を示しています。閉じた破壊発生手順において通常破壊の不均一性を最小限に抑え、誘導のトラウマの精度は説明プロトコル増加サンプル タイプに固有のパラメーターを使用して最適化。

以前私たちの研究室で使用されるギロチン 2004 年に開発された、アインホルン21で公開されたモデルに基づいていた。デザインで十分に骨の形態の任意の違いを考慮して調整を許さなかった、肢の位置決め再現性を可能にしなかった。さらに、前の装置がそれを動作するように 2 人を必要。したがって、我々 は、設計エンジニア リング、そして、新...

Watch this Scientific Journal Video about Fracture Apparatus Design and Protocol Optimization for Closed-stabilized Fractures in Rodents at JoVE.com

Fracture Apparatus Design and Protocol Optimization for Closed-stabilized Fractures in Rodents

プロトコルの目的は、コンシス テント ・ フラクチャをもたらす破壊生成パラメーターを最適化することです。このプロトコルは、ボーンのサイズと動物間に存在する形態の変化を占めています。さらに、コスト効率の高い、調節可能な破壊装置を説明します。

破壊装置設計と齧歯動物で閉じて安定骨折に対するプロトコルの最適化

The reliable generation of consistent stabilized fractures in animal models is essential for understanding the biology of bone regeneration and developing ...

fracture-apparatus-design-protocol-optimization-for-closed-stabilized

Research

JoVE Journal

Medicine

13.3K ビュー.  Michigan State University. プロトコルの目的は、コンシス テント ・ フラクチャをもたらす破壊生成パラメーターを最適化することです。このプロトコルは、ボーンのサイズと動物間に存在する形態の変化を占めています。さらに、コスト効率の高い、調節可能な破壊装置を説明します。

ビデオ: Fracture Apparatus Design and Protocol Optimization for Closed-stabilized Fractures in Rodents

Pseudofracture: An Acute Peripheral Tissue Trauma Model

Following trauma there is an early hyper-reactive inflammatory response that can lead to multiple organ dysfunction and high mortality in trauma patients; this response is often accompanied by a delayed immunosuppression that adds the clinical complications of infection and can also increase mortality.1-9 Many studies have begun to assess these changes in the reactivity of the immune system following trauma.10-15 
Immunologic studies are greatly supported through the wide variety of transgenic and knockout mice available for in vivo modeling; these strains aid in detailed investigations to assess the molecular pathways involved in the immunologic responses.16-21
The challenge in experimental murine trauma modeling is long term investigation, as fracture fixation techniques in mice, can be complex and not easily reproducible.22-30
This pseudofracture model, an easily reproduced trauma model, overcomes these difficulties by immunologically mimicking an extremity fracture environment, while allowing freedom of movement in the animals and long term survival without the continual, prolonged use of anaesthesia. The intent is to recreate the features of long bone fracture; injured muscle and soft tissue are exposed to damaged bone and bone marrow without breaking the native bone.
The pseudofracture model consists of two parts: a bilateral muscle crush injury to the hindlimbs, followed by injection of a bone solution into these injured muscles. The bone solution is prepared by harvesting the long bones from both hindlimbs of an age- and weight-matched syngeneic donor. These bones are then crushed and resuspended in phosphate buffered saline to create the bone solution.
Bilateral femur fracture is a commonly used and well-established model of extremity trauma, and was the comparative model during the development of the pseudofracture model. Among the variety of available fracture models, we chose to use a closed method of fracture with soft tissue injury as our comparison to the pseudofracture, as we wanted a sterile yet proportionally severe peripheral tissue trauma model. 31
Hemorrhagic shock is a common finding in the setting of severe trauma, and the global hypoperfusion adds a very relevant element to a trauma model. 32-36 The pseudofracture model can be easily combined with a hemorrhagic shock model for a multiple trauma model of high severity. 37

Pseudofracture, a reproducible murine model of sterile musculoskeletal trauma, allows for evaluation of late term post-traumatic immune responses. This article describes the procedural execution of the model step by step, including the potential for experimental model combinations to permit study of multiple trauma.

偽骨折：急性末梢組織外傷モデル

Following trauma there is an early hyper-reactive inflammatory response that can lead to multiple organ dysfunction and high mortality in trauma patients; ...

医学

Creating Rigidly Stabilized Fractures for Assessing Intramembranous Ossification, Distraction Osteogenesis, or Healing of Critical Sized Defects

Assessing modes of skeletal repair is essential for developing therapies to be used clinically to treat fractures. Mechanical stability plays a large role in healing of bone injuries. In the worst-case scenario mechanical instability can lead to delayed or non-union in humans. However, motion can also stimulate the healing process. In fractures that have motion cartilage forms to stabilize the fracture bone ends, and this cartilage is gradually replaced by bone through recapitulation of the developmental process of endochondral ossification. In contrast, if a bone fracture is rigidly stabilized bone forms directly via intramembranous ossification. Clinically, both endochondral and intramembranous ossification occur simultaneously. To effectively replicate this process investigators insert a pin into the medullary canal of the fractured bone as described by Bonnarens4. This experimental method provides excellent lateral stability while allowing rotational instability to persist. However, our understanding of the mechanisms that regulate these two distinct processes can also be enhanced by experimentally isolating each of these processes. We have developed a stabilization protocol that provides rotational and lateral stabilization. In this model, intramembranous ossification is the only mode of healing that is observed, and healing parameters can be compared among different strains of genetically modified mice 5-7, after application of bioactive molecules 8,9, after altering physiological parameters of healing 10, after modifying the amount or time of stabilization 11, after distraction osteogenesis 12, after creation of a non-union 13, or after creation of a critical sized defect. Here, we illustrate how to apply the modified Ilizarov fixators for studying tibial fracture healing and distraction osteogenesis in mice.

This article describes a method for stabilizing long bone fractures that is based on the application of modified Ilizarov external fixators 1-3. After application of the fixators and creation of the bone injury, healing can be assessed, distraction osteogenesis can be performed, or non-union or critical sized defect can be created and used to study therapeutic interventions.

膜内骨化、仮骨延長術、またはCriticalサイズの欠損の治癒を評価するための剛安定骨折を作成する

Assessing modes of skeletal repair is essential for developing therapies to be used clinically to treat fractures. Mechanical stability plays a large role ...

An Efficient and Reproducible Protocol for Distraction Osteogenesis in a Rat Model Leading to a Functional Regenerated Femur

This protocol describes the use of a newly developed external fixator for distraction osteogenesis in a rat femoral model. Distraction osteogenesis (DO) is a surgical technique leading to bone regeneration after an osteotomy. The osteotomized extremities are moved away from each other by gradual distraction to reach the desired elongation. This procedure is widely used in humans for lower and upper limb lengthening, treatment after a bone nonunion, or the regeneration of a bone defect following surgery for bone tumor excision, as well as in maxillofacial reconstruction. Only a few studies clearly demonstrate the efficiency of their protocol in obtaining a functional regenerated bone, i.e., bone that will support physiological weight-bearing without fracture after removal of the external fixator. Moreover, protocols for DO vary and reproducibility is limited by lack of information, making comparison between studies difficult. The aim of this study was to develop a reproducible protocol comprising an appropriate external fixator design for rat limb lengthening, with a detailed surgical technique that permits physiological weight-bearing by the animal after removal of the external fixator.

This study describes a reproducible and detailed protocol using a newly developed external fixator for distraction osteogenesis (DO) in a femoral rat model which permits physiological weight-bearing by the animal after removal of the external fixator.

機能再生大腿骨につながるラットモデルにおける仮骨延長法のための効率的かつ再現可能なプロトコル

This protocol describes the use of a newly developed external fixator for distraction osteogenesis in a rat femoral model. Distraction osteogenesis (DO) ...

生物工学

A Reliable and Reproducible Critical-Sized Segmental Femoral Defect Model in Rats Stabilized with a Custom External Fixator

Orthopedic research relies heavily on animal models to study mechanisms of bone healing in vivo as well as investigate the new treatment techniques. Critical-sized segmental defects are challenging to treat clinically, and research efforts could benefit from a reliable, ambulatory small animal model of a segmental femoral defect. In this study, we present an optimized surgical protocol for the consistent and reproducible creation of a 5 mm critical diaphyseal defect in a rat femur stabilized with an external fixator. The diaphyseal ostectomy was performed using a custom jig to place 4 Kirschner wires bicortically, which were stabilized with an adapted external fixator device. An oscillating bone saw was used to create the defect. Either a collagen sponge alone or a collagen sponge soaked in rhBMP-2 was implanted into the defect, and the bone healing was monitored over 12 weeks using radiographs. After 12 weeks, rats were sacrificed, and histological analysis was performed on the excised control and treated femurs. Bone defects containing only collagen sponge resulted in non-union, while rhBMP-2 treatment yielded the formation of a periosteal callous and new bone remodeling. Animals recovered well after implantation, and external fixation proved successful in stabilizing the femoral defects over 12 weeks. This streamlined surgical model could be readily applied to study bone healing and test new orthopedic biomaterials and regenerative therapies in vivo.

In vivo mammalian models of critical-sized bone defects are essential for researchers studying healing mechanisms and orthopedic therapies. Here, we introduce a protocol for the creation of reproducible, segmental, femoral defects in rats stabilized using external fixation.

ラットのカスタム創外固定器で安定した信頼性と再現性のある重要なサイズ分節大腿骨欠損モデル

Orthopedic research relies heavily on animal models to study mechanisms of bone healing in vivo as well as investigate the new treatment techniques. ...

A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration

Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and significantly diminish the outcome. Indeed, after routine orthopedic surgery to repair a fracture, as many as 50% of elderly patients suffer from neurologic complications like delirium. Also, the capacity to heal and regenerate tissue after surgery decreases with age, and can impact the quality of fracture repair and even osseous integration of implants. Thus, a better understanding of mechanisms that drive these age-dependent changes could provide strategic targets to minimize risk for such complications and optimize outcomes. Here, we introduce a clinically relevant mouse model of tibial fracture. The postoperative changes in these mice mimic some of the cognitive impairments commonly observed after routine orthopedic surgery in humans. Briefly, an incision is performed in the right hind limb under strictly aseptic conditions. Muscles are disassociated, and a 0.38-mm stainless steel pin is inserted into the upper crest of the tibia, inside the intramedullary canal. Osteotomy is then performed, and the wound is stapled. We have used this model to investigate the effects of surgical trauma on postoperative neuroinflammation and behavioral changes. By applying this fracture model in combination with parabiosis, a surgical model in which 2 mice are anastomosed, we have studied cells and secreted factors that systemically rejuvenate organ function and tissue regeneration after injury. By following our step-by-step protocol, these models can be reproduced with high fidelity, and can be adapted to interrogate many biologic pathways that are altered by surgical trauma.

This protocol describes a mouse model of orthopedic surgery that has been used to study mechanisms of postoperative neuroinflammation and behavioral changes, and when combined with parabiosis, to study tissue regeneration during aging.

整形外科術後の高次脳機能障害と組織再生を研究するマウス モデル

Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and ...

A Minimally Invasive Model to Analyze Endochondral Fracture Healing in Mice Under Standardized Biomechanical Conditions

Bone healing models are necessary to analyze the complex mechanisms of fracture healing to improve clinical fracture treatment. During the last decade, an increased use of mouse models in orthopedic research was noted, most probably because mouse models offer a large number of genetically-modified strains and special antibodies for the analysis of molecular mechanisms of fracture healing. To control the biomechanical conditions, well-characterized osteosynthesis techniques are mandatory, also in mice. Here, we report on the design and use of a closed bone healing model to stabilize femur fractures in mice. The intramedullary screw, made of medical-grade stainless steel, provides through fracture compression an axial and rotational stability compared to the mostly used simple intramedullary pins, which show a complete lack of axial and rotational stability. The stability achieved by the intramedullary screw allows the analysis of endochondral healing. A large amount of callus tissue, received after stabilization with the screw, offers ideal conditions to harvest tissue for biochemical and molecular analyses. A further advantage of the use of the screw is the fact that the screw can be inserted into the femur with a minimally invasive technique without inducing damage to the soft tissue. In conclusion, the screw is a unique implant that can ideally be used in closed fracture healing models offering standardized biomechanical conditions.

This protocol describes a minimally invasive osteosynthesis technique using an intramedullary screw for standardized stabilization of femur fractures, which can be used to analyze endochondral bone healing in mice.

癒しの標準化された生体力学的条件下でマウスの軟骨破壊を分析する低侵襲モデル

Bone healing models are necessary to analyze the complex mechanisms of fracture healing to improve clinical fracture treatment. During the last decade, an ...

The Generation of Closed Femoral Fractures in Mice: A Model to Study Bone Healing

Bone fractures impose a tremendous socio-economic burden on patients, in addition to significantly affecting their quality of life. Therapeutic strategies that promote efficient bone healing are non-existent and in high demand. Effective and reproducible animal models of fractures healing are needed to understand the complex biological processes associated with bone regeneration. Many animal models of fracture healing have been generated over the years; however, murine fracture models have recently emerged as powerful tools to study bone healing. A variety of open and closed models have been developed, but the closed femoral fracture model stands out as a simple method for generating rapid and reproducible results in a physiologically relevant manner. The goal of this surgical protocol is to generate unilateral closed femoral fractures in mice and facilitate a post-fracture stabilization of the femur by inserting an intramedullary steel rod. Although devices such as a nail or a screw offer greater axial and rotational stability, the use of an intramedullary rod provides a sufficient stabilization for consistent healing outcomes without producing new defects in the bone tissue or damaging nearby soft tissue. Radiographic imaging is used to monitor the progression of callus formation, bony union, and subsequent remodeling of the bony callus. Bone healing outcomes are typically associated with the strength of the healed bone and measured with torsional testing. Still, understanding the early cellular and molecular events associated with fracture repair is critical in the study of bone tissue regeneration. The closed femoral fracture model in mice with intramedullary fixation serves as an attractive platform to study bone fracture healing and evaluate therapeutic strategies to accelerate healing.

The murine closed femoral fracture model is a powerful platform to study fracture healing and novel therapeutic strategies to accelerate bone regeneration. The goal of this surgical protocol is to generate unilateral closed femoral fractures in mice using an intramedullary steel rod to stabilize the femur.

マウスで閉じた大腿骨骨折の生成: 骨の治癒を研究するためのモデル

Bone fractures impose a tremendous socio-economic burden on patients, in addition to significantly affecting their quality of life. Therapeutic strategies ...

Protocol for Developing a Femur Osteotomy Model in Wistar Albino Rats

Fracture healing is a physiological process resulting in the regeneration of bone defects by the coordinated action of osteoblasts and osteoclasts. Osteoanabolic drugs have the potential to augment the repair of fractures but have constraints like high costs or undesirable side effects. The bone healing potential of a drug can initially be determined by in vitro studies, but in vivo studies are needed for the final proof of concept. Our objective was to develop a femur osteotomy rodent model that could help researchers understand the development of callus formation following fracture of the shaft of the femur and that could help establish whether a potential drug has bone healing properties. Adult male Wistar albino rats were used after Institutional Animal Ethics Committee clearance. The rodents were anesthetized, and under aseptic conditions, complete transverse fractures at the middle one-third of the shafts of the femurs were created using open osteotomy. The fractures were reduced and internally fixed using intramedullary K-wires, and secondary fracture healing was allowed to take place. After surgery, intraperitoneal analgesics and antibiotics were given for 5 days. Sequential weekly x-rays assessed callus formation. The rats were sacrificed based on radiologically pre-determined time points, and the development of the fracture callus was analyzed radiologically and using immunohistochemistry.

Here, we present a protocol to iatrogenically fracture the shaft of the femur of Wistar albino rats and follow up on the development of the callus. This femur osteotomy model can help researchers evaluate the process of fracture healing and to study how a drug could influence fracture healing.

Wistarアルビノラットにおける大腿骨骨切り術モデルを開発するためのプロトコル

Fracture healing is a physiological process resulting in the regeneration of bone defects by the coordinated action of osteoblasts and osteoclasts. ...

Transverse Fracture of the Mouse Femur with Stabilizing Pin

Fracture repair is an essential function of the skeleton that cannot be reliably modeled in vitro. A mouse injury model is an efficient approach to test whether a gene, gene product or drug influences bone repair because murine bones recapitulate the stages observed during human fracture healing. When a mouse or human breaks a bone, an inflammatory response is initiated, and the periosteum, a stem cell niche surrounding the bone itself, is activated and expands. Cells residing in the periosteum then differentiate to form a vascularized soft callus. The transition from the soft callus to a hard callus occurs as the recruited skeletal progenitor cells differentiate into mineralizing cells, and the bridging of the fractured ends results in the bone union. The mineralized callus then undergoes remodeling to restore the original shape and structure of the healed bone. Fracture healing has been studied in mice using various injury models. Still, the best way to recapitulate this entire biological process is to break through the cross-section of a long bone that encompasses both cortices. This protocol describes how a stabilized, transverse femur fracture can be safely performed to assess healing in adult mice. A surgical protocol including detailed harvesting and imaging techniques to characterize the different stages of fracture healing is also provided.

This protocol describes a method to perform fractures on adult mice and monitor the healing process.

安定化ピン付きマウス大腿骨の横骨折

Fracture repair is an essential function of the skeleton that cannot be reliably modeled in vitro. A mouse injury model is an efficient approach to test ...

生物学

Establishing a Diaphyseal Femur Fracture Model in Mice

Bones have a significant regenerative capacity. However, fracture healing is a complex process, and depending on the severity of the lesions and the age and overall health status of the patient, failures can occur, leading to delayed union or nonunion. Due to the increasing number of fractures resulting from high-energy trauma and aging, the development of innovative therapeutic strategies to improve bone repair based on the combination of skeletal/mesenchymal stem/stromal cells and biomimetic biomaterials is urgently needed. To this end, the use of reliable animal models is fundamental to better understanding the key cellular and molecular mechanisms that determine the healing outcomes. Of all the models, the mouse is the preferred research model because it offers a wide variety of transgenic strains and reagents for experimental analysis. However, the establishment of fractures in mice may be technically challenging due to their small size. Therefore, this article aims to demonstrate the procedures for the surgical establishment of a diaphyseal femur fracture in mice, which is stabilized with an intramedullary wire and resembles the most common bone repair process, through cartilaginous callus formation.

This protocol describes a surgical procedure for the establishment of a diaphyseal fracture in the femur of mice, which is stabilized with an intramedullary wire, for fracture healing studies.

マウスにおける骨幹大腿骨骨折モデルの確立

Bones have a significant regenerative capacity. However, fracture healing is a complex process, and depending on the severity of the lesions and the age ...

破壊装置設計と齧歯動物で閉じて安定骨折に対するプロトコルの最適化

要約

さらに動画を探す

偽骨折：急性末梢組織外傷モデル

膜内骨化、仮骨延長術、またはCriticalサイズの欠損の治癒を評価するための剛安定骨折を作成する

機能再生大腿骨につながるラットモデルにおける仮骨延長法のための効率的かつ再現可能なプロトコル

ラットのカスタム創外固定器で安定した信頼性と再現性のある重要なサイズ分節大腿骨欠損モデル

整形外科術後の高次脳機能障害と組織再生を研究するマウスモデル

癒しの標準化された生体力学的条件下でマウスの軟骨破壊を分析する低侵襲モデル

マウスで閉じた大腿骨骨折の生成: 骨の治癒を研究するためのモデル

Wistarアルビノラットにおける大腿骨骨切り術モデルを開発するためのプロトコル

安定化ピン付きマウス大腿骨の横骨折

マウスにおける骨幹大腿骨骨折モデルの確立

破壊装置設計と齧歯動物で閉じて安定骨折に対するプロトコルの最適化

要約

さらに動画を探す

偽骨折：急性末梢組織外傷モデル

膜内骨化、仮骨延長術、またはCriticalサイズの欠損の治癒を評価するための剛安定骨折を作成する

機能再生大腿骨につながるラットモデルにおける仮骨延長法のための効率的かつ再現可能なプロトコル

ラットのカスタム創外固定器で安定した信頼性と再現性のある重要なサイズ分節大腿骨欠損モデル

整形外科術後の高次脳機能障害と組織再生を研究するマウス モデル

癒しの標準化された生体力学的条件下でマウスの軟骨破壊を分析する低侵襲モデル

マウスで閉じた大腿骨骨折の生成: 骨の治癒を研究するためのモデル

Wistarアルビノラットにおける大腿骨骨切り術モデルを開発するためのプロトコル

安定化ピン付きマウス大腿骨の横骨折

マウスにおける骨幹大腿骨骨折モデルの確立

整形外科術後の高次脳機能障害と組織再生を研究するマウスモデル