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、および遺伝子型) に基づく破壊基準を確立する共通の破壊データベースの作成を有効にします。破壊変数の最適化試料の不均質 - 無駄な時間、失われたリソース、および使用不可能なデータの量を減らすが大幅に減少します。
正確かつ正確な骨折を生成するには、標準化された一連の特異性の高度を生産し、破壊の場所の可変性を減らす破壊生成パラメーターを確立することが重要です。破壊発生に加えて、適切な安定化も破壊カルス形成を促進して非組合員の確率を減らすために必要です。髄内固定実験的および臨床的に四肢の長管骨骨折を安定させるために使用される一般的な固定方法です。内部的に執着骨折が直接組織分化、破面で骨吸収を伴うプロセスの回復しない傾向があり、組合経由でその後破壊のカルス形成および改造します。これらのプロセスは、破壊接合部で運動と髄腔内ピンの移行によって妨げられることができます。このプロトコルは、骨折部位の固定の後で変位の程度を削減し洗練された手術機器や技術の不必要な被害を引き起こす可能性が使用せずピン移行の範囲を制限固定方式を利用します。皮質骨の組織。特定のサンプルの種類ごとの髄内接触を最大化する pin パラメーターのセットを生成する適切なカルス形成と骨改造の必要な安定性を提供します。
髄内ピンが配置されると、次の重要なステップは単純横骨折を生成します。骨折を介して適用外部から鈍力外傷を生成するプロトコルには、粉砕骨折を生成し、固定ハードウェアに損傷を与える可能性があります。これらの合併症を軽減するため、各サンプル セット23の平均皮質直径 x 0.5 に等しくなるように、影響の深さを制御することが重要です。破壊粉砕は、外部の鈍力外傷処置中に無理な力に起因できます。影響の速度は、重大なしきい値を超えた場合、き裂伝播速度は複数破壊サイト24で生じる応力波を生成します。応力波の生産の粉砕の可能性を減らすための衝撃速度しきい値以下ながらも、破断が生じるに十分な運動エネルギーを生成する ram の体重とドロップ高さを確立する重要です。高衝撃速度は、前に生成された25は骨折は、過剰なエネルギー吸収を生成する骨の急速載荷になります。破壊伝播時に読み込み中に吸収される過剰なエネルギーが解放される非直線的粉砕が生成されます。低衝撃速度とエネルギーの読み込みが遅い、生産高衝撃速度と急速載荷26に比べて線形破壊の確率が高い。粉砕の発生率を最小限に抑えるためにこのプロトコルはマウスの標準 ram 重量 250 g を使用する - これはより大きい種に合わせて調整することができます。非常に若い動物または知られている骨の病気 (例えば、骨または骨硬化症) とのそれらを作業するとき ram 体重減少する必要があります。ドロップの高さだけ 1 つの変数を調整することが同時に最適化されているときに一貫性のある ram の重量を使用することが重要です。種特異的な理想的な衝撃速度の計算は供試体の軟組織形態とサイズのわずかな変化のための会計でより一貫性のある骨折を生成します。
上記の方法は他の破壊世代プロトコルの多くの欠点を排除します。ただし、いくつかの側面は、効率的に目的の結果を生成する訓練を必要があります。プロシージャの 1 つの可能な合併症は、かなり骨や軟部組織の損傷を引き起こす可能性があります、不正確なピン配置です。これは主に、アプローチの限られた可視性と十分な二国間の手の器用さの欠如です。オープン切開せず内部固定は、プロシージャを実行するユーザーからスキルのかなりの量を要求できます。したがって、それは彼または彼女に持っている十分な訓練 - 死体、癒しのプロセス全体で合併症を引き起こすことができる余分な軟部組織の損傷を避けるために - 必要な場合重要です。(膝蓋靭帯、脛骨プラトーおよび大腿骨の顆間ノッチ) プロトコルで指定されている構造を認識し最小限の軟部組織損傷と一貫性のある、正確な固定を出す助けになります。ただし、説明研究の目標は、ピン配置の詳細な手順を提示すること、むしろ理想的な骨折を生成するメソッドを記述します。
近位端、大腿骨または脛骨の遠位端のを介して任意のリーマを避けるためにカッティング ゲージの使用が勧めします。大腿骨の近位端をドリルと、軟部組織への不必要な損傷を引き起こすか、治癒過程におけるモビリティと損傷の合併症を引き起こして、股関節の骨。同様に、脛骨の遠位端をリーマと足首の構造、歩行力学、読み込み、およびカルス形成を変更することが損傷します。
破壊位置の精度を高めるため、デバイス内肢の適切なポジショニングを確認するカスタム肢位置決め治具を設計できます。正確かつ正確な衝撃は一貫して目的の場所に骨折を生成に不可欠です。当研究室は、現在 2 つの治具を採用しています: - 脛骨骨折と半ば大腿骨骨折ですがモジュラー設計および 3 D 印刷の汎用性のための他の 1 つはさまざまな場所で骨折を生成する機能の研究者を与えます。特定の場所に骨折を生成するように設計カスタム治具の追加は、オペレーターのエラーの可能性を制限することによって精度と破壊発生の精度の両方を増加します。
このメソッドのほとんどの制限は、他の既存の閉じた破砕技術において直面する問題に似ていません。過度の軟部組織や脂肪高齢や肥満のマウスに見られるように、骨折の発生が低下します。これは通常力のしていない影響を与える深さの欠如不足のために注意することが重要です。この制限は、ram の重量や骨折部位に適用される運動エネルギーを増加する速度を増やすことによって克服できます。このメソッドは、内部固定に骨の骨内表面を混乱させるし、治癒に影響を与えることができますにも依存します。骨破壊も発生すると臨床的に髄内釘、骨折整復する内の貢献を検討している場合、創外固定やプレートより良いオプションが可能性があります。追加の制限は、初期パラメーターを確立するいけにえの動物の必要なサンプルただし、破壊変数より多くのサンプルの種類を確立データベースを開発すると、その他のいけにえサンプルの必要性が減少します。
記述のプロトコルは、閉じた破壊生成手順で通常見られる破壊の不均一性を最小限に抑え、サンプル タイプに固有の標準化されたパラメーターを使用することによるトラウマの精度を向上します。最新破壊世代プロトコル マウス種のみに適用されますで、適度にコンシス テントなフラクチャします。彼らは頻繁に最適な結果を得るための特定のサンプル タイプを使用する必要や、系統内の変化を考慮しません。プロトコルはマウス系統間に存在可能性があります、他の種でコンシス テント ・ フラクチャを生成に対応できるサイズや骨の形態変化のアカウントをここで紹介します。さらに、このプロトコルの広範な応用は研究者間の標準化された破壊言語の採用をサポートします。一般的な変数と類似したプロトコルを使用してメソッドの一貫性を改善し、研究間の比較を強化します。さらに集団破壊生成パラメーターの汎用性を高める追加破壊モデルで使用される破壊の最適化のプロトコルの可能性がある、上記で説明したパラメーターはマウス長管骨を特定、データベース。この破壊最適化プロトコルを用いたは破壊位置とパターンの整合性を向上させることにより均一な使用可能なサンプルの生産を増やします。サンプルのより高いパーセントの利回りが実験室のリソースの無駄を省き、必要な動物の数を減らすし、研究効率を向上させます。

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 border="0" cellpadding="0" cellspacing="0" style="width:911px;" width="910">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="20">
			<td height="20" style="height:20px;width:240px;">Support Subassembly</td>
			<td style="width:209px;"></td>
			<td style="width:147px;"></td>
			<td style="width:315px;">Supplementary Figure 1</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Beam, Support--Jaw Section&#160;</td>
			<td style="width:209px;">80/20</td>
			<td>1003 x 9.00</td>
			<td>w/ #7042 at A, C, in Left End</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Beam, Support--Horizontal Section</td>
			<td style="width:209px;">80/20</td>
			<td>1002 x 14.00</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Beam, Support--Vertical 1</td>
			<td style="width:209px;">80/20</td>
			<td>1050 x 10.50&#160;</td>
			<td>w/ #7042 at A in Left End and at A in Right End</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Beam, Support--Vertical 2</td>
			<td style="width:209px;">80/20</td>
			<td>1010 x 10.50&#160;</td>
			<td>w/ #7042 at D, B in Left End and at A in Right End</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Beam, Support--Plate Mount</td>
			<td style="width:209px;">80/20</td>
			<td>1030 x 8.00&#160;</td>
			<td>w/ #7036 at Left End</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Beam, Support--Magnet</td>
			<td style="width:209px;">80/20</td>
			<td>1010 x 13.50&#160;</td>
			<td>w/ #7042 at A, C, in Right End</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Anchors (3)</td>
			<td style="width:209px;">80/20</td>
			<td style="width:147px;">3392</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Double Anchor (3)</td>
			<td style="width:209px;">80/20</td>
			<td style="width:147px;">3091</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Bolt Assembly (6)</td>
			<td style="width:209px;">80/20</td>
			<td style="width:147px;">3386</td>
			<td>1/4-20 x 3/8&#34;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Button Head Socket Cap Screw (6)</td>
			<td style="width:209px;">80/20</td>
			<td style="width:147px;">3604</td>
			<td>1/4-20 x 3/4&#34;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Ram Subassembly</td>
			<td style="width:209px;"></td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 2</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Block, Stop</td>
			<td style="width:209px;">Custom</td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 3</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Block, Guide</td>
			<td style="width:209px;">Custom</td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 3</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Rod, Ram</td>
			<td style="width:209px;">Custom</td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 4</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Alignment Screw</td>
			<td style="width:209px;">Custom</td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 5</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Plate, Mounting</td>
			<td style="width:209px;">Custom</td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 6</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Linear Sleeve Bearing (2)</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td style="width:147px;">8649T2</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Hex Nut (3)</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td>92673A125</td>
			<td>3/8-16 UNC</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Socket Cap Screw (8)</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td style="width:147px;">92196A108</td>
			<td>4/40 x 3/8&#34;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Socket Cap Screw (6)</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td style="width:147px;">92196A032</td>
			<td>4/40 x 1 1/8&#34;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Socket Cap Screw (1)</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td style="width:147px;">92196A267&#160;</td>
			<td>10/32 3/8&#34;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Magnet Subassembly</td>
			<td style="width:209px;"></td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 7</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Mount, Magnet</td>
			<td style="width:209px;">Custom</td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 8</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Power Supply</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td>70235K23</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Foot Switch</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td>7376k2</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Electromagnet</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td>5698k111</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Wire - 10 feet</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td style="width:147px;">9936k12</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Rod, Magnet</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td>95412A566</td>
			<td>1/4&#34; Threaded Rod x 7&#34;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Corner Bracket (6)</td>
			<td style="width:209px;">80/20</td>
			<td style="width:147px;">4108</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Socket Cap Screw (1)</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td style="width:147px;">92196A705</td>
			<td>10/32 1 1/4&#34;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Hex Nut (4)</td>
			<td style="width:209px;">McMaster-Carr</td>
			<td>92673A113</td>
			<td>1/4-20 UNC</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Complete Assembly</td>
			<td style="width:209px;"></td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 9</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Bracket, Leg Jaw (2)</td>
			<td style="width:209px;">Custom</td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 10</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Platform, Fracture</td>
			<td style="width:209px;">Custom</td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 11</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Jig, Positioning-Fracture</td>
			<td style="width:209px;">Custom</td>
			<td style="width:147px;"></td>
			<td>Supplementary Figure 12</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Other</td>
			<td style="width:209px;"></td>
			<td style="width:147px;"></td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Pin Cutter</td>
			<td style="width:209px;">Medical Supplies and Equipment</td>
			<td style="width:147px;">150S</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;width:240px;">Needles</td>
			<td style="width:209px;">Sigma</td>
			<td style="width:147px;">Z192430, Z192376&#160;</td>
			<td>23g x 1.5&#34; - mouse femur, 27g x 1.25&#34; - 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。

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

Nanyang Technological University

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

The Use of Cystometry in Small Rodents: A Study of Bladder Chemosensation

The lower urinary tract (LUT) functions as a dynamic reservoir that is able to store urine and to efficiently expel it at a convenient time. While storing urine, however, the bladder is exposed for prolonged periods to waste products. By acting as a tight barrier, the epithelial lining of the LUT, the urothelium, avoids re-absorption of harmful substances. Moreover, noxious chemicals stimulate the bladder's nociceptive innervation and initiate voiding contractions that expel the bladder's contents. Interestingly, the bladder's sensitivity to noxious chemicals has been used successfully in clinical practice, by intravesically infusing the TRPV1 agonist capsaicin to treat neurogenic bladder overactivity1. This underscores the advantage of viewing the bladder as a chemosensory organ and prompts for further clinical research. However, ethical issues severely limit the possibilities to perform, in human subjects, the invasive measurements that are necessary to unravel the molecular bases of LUT clinical pharmacology. A way to overcome this limitation is the use of several animal models2. Here we describe the implementation of cystometry in mice and rats, a technique that allows measuring the intravesical pressure in conditions of controlled bladder perfusion.
	After laparotomy, a catheter is implanted in the bladder dome and tunneled subcutaneously to the interscapular region. Then the bladder can be filled at a controlled rate, while the urethra is left free for micturition. During the repetitive cycles of filling and voiding, intravesical pressure can be measured via the implanted catheter. As such, the pressure changes can be quantified and analyzed. Moreover, simultaneous measurement of the voided volume allows distinguishing voiding contractions from non-voiding contractions3.
	Importantly, due to the differences in micturition control between rodents and humans, cystometric measurements in these animals have only limited translational value4. Nevertheless, they are quite instrumental in the study of bladder pathophysiology and pharmacology in experimental pre-clinical settings. Recent research using this technique has revealed the key role of novel molecular players in the mechano- and chemo-sensory properties of the bladder.

Cystometry is an efficient technique to measure bladder function of small animals in vivo. The bladder is continuously infused at rates controlled through an intravesical catheter, whereas the urethra is left free for micturition. This allows for repetitive filling and emptying of the bladder, while intravesical pressure and voided volume are recorded.

小型げっ歯類における膀胱内圧測定の使用：膀胱Chemosensationの研究

	The lower urinary tract (LUT) functions as a  dynamic reservoir that is able to store urine and to efficiently expel it at a  convenient time. While ...

医学

Collection Protocol for Human Pancreas

This dissection and sampling procedure was developed for the Network for Pancreatic Organ Donors with Diabetes (nPOD) program to standardize preparation of pancreas recovered from cadaveric organ donors. The pancreas is divided into 3 main regions (head, body, tail) followed by serial transverse sections throughout the medial to lateral axis. Alternating sections are used for fixed paraffin and fresh frozen blocks and remnant samples are minced for snap frozen sample preparations, either with or without RNAse inhibitors, for DNA, RNA, or protein isolation. The overall goal of the pancreas dissection procedure is to sample the entire pancreas while maintaining anatomical orientation.
Endocrine cell heterogeneity in terms of islet composition, size, and numbers is reported for human islets compared to rodent islets 1. The majority of human islets from the pancreas head, body and tail regions are composed of insulin-containing &beta;-cells followed by lower proportions of glucagon-containing &alpha;-cells and somatostatin-containing &delta;-cells. Pancreatic polypeptide-containing PP cells and ghrelin-containing epsilon cells are also present but in small numbers. In contrast, the uncinate region contains islets that are primarily composed of pancreatic polypeptide-containing PP cells 2. These regional islet variations arise from developmental differences. The pancreas develops from the ventral and dorsal pancreatic buds in the foregut and after rotation of the stomach and duodenum, the ventral lobe moves and fuses with the dorsal 3. The ventral lobe forms the posterior portion of the head including the uncinate process while the dorsal lobe gives rise to the rest of the organ. Regional pancreatic variation is also reported with the tail region having higher islet density compared to other regions and the dorsal lobe-derived components undergoing selective atrophy in type 1 diabetes4,5.
Additional organs and tissues are often recovered from the organ donors and include pancreatic lymph nodes, spleen and non-pancreatic lymph nodes. These samples are recovered with similar formats as for the pancreas with the addition of isolation of cryopreserved cells. When the proximal duodenum is included with the pancreas, duodenal mucosa may be collected for paraffin and frozen blocks and minced snap frozen preparations.

This video demonstrates a dissection procedure for processing human pancreas into multiple storage formats. Anatomical orientation is maintained throughout the pancreatic regions to allow definition of regional islet composition and density.

ヒト膵臓の収集プロトコル

This dissection and sampling procedure was developed for the Network for Pancreatic Organ Donors with Diabetes (nPOD) program to standardize preparation ...

Parabiosis in Mice: A Detailed Protocol

Parabiosis is a surgical union of two organisms allowing sharing of the blood circulation. Attaching the skin of two animals promotes formation of microvasculature at the site of inflammation. Parabiotic partners share their circulating antigens and thus are free of adverse immune reaction. First described by Paul Bert in 18641, the parabiosis surgery was refined by Bunster and Meyer in 1933 to improve animal survival2. In the current protocol, two mice are surgically joined following a modification of the Bunster and Meyer technique. Animals are connected through the elbow and knee joints followed by attachment of the skin allowing firm support that prevents strain on the sutured skin. Herein, we describe in detail the parabiotic joining of a ubiquitous GFP expressing mouse to a wild type (WT) mouse. Two weeks after the procedure, the pair is separated and GFP positive cells can be detected by flow cytometric analysis in the blood circulation of the WT mouse. The blood chimerism allows one to examine the contribution of the circulating cells from one animal in the other.

Parabiotic joining of two organisms leads to the development of a shared circulatory system. In this protocol, we describe the surgical steps to form a parabiotic connection between a wild-type mouse and a constitutive GFP-expressing mouse.

マウスの並体結合：詳細なプロトコル

Parabiosis is a surgical union of two organisms allowing sharing of the blood circulation. Attaching the skin of two animals promotes formation of ...

Cell-based Assay Protocol for the Prognostic Prediction of Idiopathic Scoliosis Using Cellular Dielectric Spectroscopy

This protocol details the experimental and analytical procedure for a cell-based assay developed in our laboratory as a functional test to predict the prognosis of idiopathic scoliosis in asymptomatic and affected children. The assay consists of the evaluation of the functional status of Gi and Gs proteins in peripheral blood mononuclear cells (PBMCs) by cellular dielectric spectroscopy (CDS), using an automated CDS-based instrument, and the classification of children into three functional groups (FG1, FG2, FG3) with respect to the profile of imbalance between the degree of response to Gi and Gs proteins stimulation. The classification is further confirmed by the differential effect of osteopontin (OPN) on response to Gi stimulation among groups and the severe progression of disease is referenced by FG2. Approximately, a volume of 10 ml of blood is required to extract PBMCs by Ficoll-gradient and cells are then stored in liquid nitrogen. The adequate number of PBMCs to perform the assay is obtained after two days of cell culture. Essentially, cells are first incubated with phytohemmaglutinin (PHA). After 24 hr incubation, medium is replaced by a PHA-free culture medium for an additional 24 hr prior to cell seeding and OPN treatment. Cells are then spectroscopically screened for their responses to somatostatin and isoproterenol, which respectively activate Gi and Gs proteins through their cognate receptors. Both somatostatin and isoproterenol are simultaneously injected with an integrated fluidics system and the cells&#39; responses are monitored for 15 min. The assay can be performed with fresh or frozen PBMCs and the procedure is completed within 4 days.

A structured protocol is presented for a cell-based assay as a functional test to predict the prognosis of idiopathic scoliosis using cellular dielectric spectroscopy (CDS). The assay can be performed with fresh or frozen peripheral blood mononuclear cells (PBMCs) and the procedure is completed within 4 days.

携帯誘電分光法による特発性側弯症の予後予測のための細胞ベースのアッセイプロトコール

This protocol details the experimental and analytical procedure for a cell-based assay developed in our laboratory as a functional test to predict the ...

Sequential In vivo Imaging of Osteogenic Stem/Progenitor Cells During Fracture Repair

Bone turns over continuously and is highly regenerative following injury. Osteogenic stem/progenitor cells have long been hypothesized to exist, but in vivo demonstration of such cells has only recently been attained. Here, in vivo imaging techniques to investigate the role of endogenous osteogenic stem/progenitor cells (OSPCs) and their progeny in bone repair are provided. Using osteo-lineage cell tracing models and intravital imaging of induced microfractures in calvarial bone, OSPCs can be directly observed during the first few days after injury, in which critical events in the early repair process occur. Injury sites can be sequentially imaged revealing that OSPCs relocate to the injury, increase in number and differentiate into bone forming osteoblasts. These methods offer a means of investigating the role of stem cell-intrinsic and extrinsic molecular regulators for bone regeneration and repair.

Sequential In vivo Imaging of Osteogenic Stem/Progenitor Cells During Fracture Repair

Quantitative measurement of bone progenitor function in fracture healing requires high resolution serial imaging technology. Here, protocols are provided for using intravital microscopy and osteo-lineage tracking to sequentially image and quantify the migration, proliferation and differentiation of endogenous osteogenic stem/progenitor cells in the process of repairing bone fracture.

シーケンシャル<em&gt;インビボ</em&gt;骨折修復中に、骨形成幹細胞/前駆細胞のイメージング

Bone turns over continuously and is highly regenerative following injury. Osteogenic stem/progenitor cells have long been hypothesized to exist, but in ...

Catheterization of the Carotid Artery and Jugular Vein to Perform Hemodynamic Measures, Infusions and Blood Sampling in a Conscious Rat Model

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. Intra-tracheal inoculation of a known amount of bacteria has been successfully used to reproduce the pathogenesis of pneumonia which then develops into sepsis. Monitoring hemodynamic parameters and providing standard clinical treatment including infusion of antibiotics, fluids and drugs to maintain blood pressure is critical to simulate routine supportive care in this model but to do so requires both arterial and venous vascular access. The video details the surgical technique for implanting carotid artery and common jugular vein catheters in an anesthetized rat. Following a 72 hr recovery period, the animals will be re-anesthetized and connected to a tether and swivel setup attached to the rodent housing which connects the implanted catheters to the hemodynamic monitoring system. This setup allows free movement of the rat during the study while continuously monitoring pressures, infusing fluids and drugs (antibiotics, vasopressors) and performing blood sampling.

Vascular accesses to measure hemodynamics, provide fluids and perform blood sampling are important to any small animal model study. We present a technique for implanting catheters into the carotid artery and the common jugular vein in an anesthetized rat for connecting to a system to perform monitoring, infusions and sampling.

配慮ラットモデルにおける血行動態の措置、煎茶や血液サンプリングを実行するために頸動脈と頸静脈のカテーテル

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. ...

Nerve-sparing Mid-urethral Obstruction (NeMO) in Female Small Rodents

Partial bladder outlet obstruction (pBOO) has a high prevalence, causes significant patient burden, and immense health care costs. The most common animal model to investigate bladder remodeling in pBOO are female rodents undergoing partial obstruction at the proximal urethra. Variability in the degree of obstruction and animal mortality are major concerns with proximal obstruction. Furthermore, dissecting around the proximal urethra and bladder neck jeopardizes bladder innervation.
We developed a nerve-sparing mid-urethral obstruction (NeMO) model for pBOO avoiding the disadvantages of the traditional model. We approached the urethra just inferior to the pubic symphysis, which obviated the need for laparotomy as well as for dissection in this area; also, the striated urethral sphincter remained untouched. We performed NeMO in female Sprague-Dawley rats (12 obstructions, 6 sham animals) as well as in female C57/bl6 mice (20 obstructions, 18 sham animals). After two weeks, we evaluated bladder function, bladder mass, and body mass.
We had no mortalities among obstructed- or sham-operated female rats; as described for the traditional proximal pBOO-method, we tied the suture around the proximal urethra and a temporarily placed 0.9 mm metal rod. NeMO induced an 85% increase in bladder mass after two weeks, average residual urine volume was 0.4 mL in partially obstructed rats while only 0.03 mL in sham animals. In mice, we tested 3 sizes of cannulas that we placed along the urethra when tying the suture. We found that using a 27-gauge cannula resulted in over 50% animal mortality; placing the 25-gauge cannula did not yield the desired response in increasing bladder mass; utilizing a 26-gauge cannula yielded favorable results with minimal animal mortality (1/8) yet a significant 2-fold increase in bladder mass.

Nerve-sparing Mid-urethral Obstruction NeMO in Female Small Rodents

Traditional modeling of partial bladder outlet obstruction in rodents is fraught with animal mortality. A denervation injury from dissection around the proximal urethra and bladder neck is also of major concern. We developed and evaluated a safe and reliable mid-urethral obstruction model, avoiding the shortcomings of the traditional model.

女性の小型げっ歯類における神経温存ミッド尿道閉塞（NEMO）

Partial bladder outlet obstruction (pBOO) has a high prevalence, causes significant patient burden, and immense health care costs. The most common animal ...

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur

Endochondral fracture healing is a complex process involving the development of fibrous, cartilaginous, and osseous tissue in the fracture callus. The amount of the different tissues in the callus provides important information on the fracture healing progress. Available in vivo techniques to longitudinally monitor the callus tissue development in preclinical fracture-healing studies using small animals include digital radiography and &#181;CT imaging. However, both techniques are only able to distinguish between mineralized and non-mineralized tissue. Consequently, it is impossible to discriminate cartilage from fibrous tissue. In contrast, magnetic resonance imaging (MRI) visualizes anatomical structures based on their water content and might therefore be able to noninvasively identify soft tissue and cartilage in the fracture callus. Here, we report the use of an MRI-compatible external fixator for the mouse femur to allow MRI scans during bone regeneration in mice. The experiments demonstrated that the fixator and a custom-made mounting device allow repetitive MRI scans, thus enabling longitudinal analysis of fracture-callus tissue development.

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur

The evaluation of tissue development in the fracture callus during endochondral bone healing is essential to monitor the healing process. Here, we report the use of a magnetic resonance imaging (MRI)-compatible external fixator for the mouse femur to allow MRI scans during bone regeneration in mice.

生体内で破壊カルス開発マウス大腿骨の骨、MRI 対応のデバイスを用いたマウスの骨治癒過程の評価

Endochondral fracture healing is a complex process involving the development of fibrous, cartilaginous, and osseous tissue in the fracture callus. The ...

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 ...