Joey P Johnson1, Christopher T Born2, Nathan Thomas3, Jeremy Truntzer4, P Kaveh Mansuripur2, Justin Kleiner3, Scott T McAlister2, Dioscaris Garcia2, Sarath Koruprolu2. 1. Department of Orthopedic Surgery, Loma Linda University, 11406 Loma Linda Drive, Suite 128, Loma Linda, CA, 92354, USA. 2. Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI, 593 Eddy Street, Providence, RI, 02903, USA. 3. Warren Alpert Medical School of Brown University, 222 Richmond Street, Providence, RI, 02912, USA. 4. Department of Orthopedic Surgery, Stanford University, 291 University Drive, Stanford, CA, 94305, USA.
Abstract
BACKGROUND: Animal models have been used for decades to simulate human fractures in the laboratory setting. Fracture models in mice are attractive because they offer a high volume, relatively low-cost method of investigating fracture healing characteristics. We report on the development of a novel murine femur fracture model that is rapid, reproducible and inexpensive. METHODS: As part of a pilot study to investigate the effects of smoking on fracture healing, fifteen 35-43 g twelve-week old female CD-1 mice underwent a novel surgical protocol using direct visualization of femur fracture creation and fixation. Following surgery, mice were sacrificed at 14 days, 28 days and 42 days. After sacrifice, the femora were analyzed using MicroCT and histology to evaluate progression of healing. RESULTS: Of the 14 mice that survived the surgical procedure (one succumbed to a complication of anesthesia), two lost reduction and did not heal. Histology demonstrated at 14 days 44.1% (SD±2.9%) of callus composed of cartilage. At 28 days there was 19.0% (SD±3.4%) of callus composed of cartilage. At 42 days there was 8.4% (SD±2.6%) callus composed of cartilage (p < 0.005). MicroCT demonstrated that from 14 to 42 days the average callus volume decreased from 101.6 mm3 to 68.2 mm3 while the relative bone volume of callus increased from 14 to 42 days (15%-31%) (p = 0.068). CONCLUSIONS: Our novel fracture and fixation model is an effective, rapid, reproducible and inexpensive method to simulate a fracture in a laboratory setting. Additionally, our model reliably creates a reproducible progression of radiographic and histological bone healing.
BACKGROUND: Animal models have been used for decades to simulate human fractures in the laboratory setting. Fracture models in mice are attractive because they offer a high volume, relatively low-cost method of investigating fracture healing characteristics. We report on the development of a novel murine femur fracture model that is rapid, reproducible and inexpensive. METHODS: As part of a pilot study to investigate the effects of smoking on fracture healing, fifteen 35-43 g twelve-week old female CD-1 mice underwent a novel surgical protocol using direct visualization of femur fracture creation and fixation. Following surgery, mice were sacrificed at 14 days, 28 days and 42 days. After sacrifice, the femora were analyzed using MicroCT and histology to evaluate progression of healing. RESULTS: Of the 14 mice that survived the surgical procedure (one succumbed to a complication of anesthesia), two lost reduction and did not heal. Histology demonstrated at 14 days 44.1% (SD±2.9%) of callus composed of cartilage. At 28 days there was 19.0% (SD±3.4%) of callus composed of cartilage. At 42 days there was 8.4% (SD±2.6%) callus composed of cartilage (p < 0.005). MicroCT demonstrated that from 14 to 42 days the average callus volume decreased from 101.6 mm3 to 68.2 mm3 while the relative bone volume of callus increased from 14 to 42 days (15%-31%) (p = 0.068). CONCLUSIONS: Our novel fracture and fixation model is an effective, rapid, reproducible and inexpensive method to simulate a fracture in a laboratory setting. Additionally, our model reliably creates a reproducible progression of radiographic and histological bone healing.
Authors: Moritz Klein; Andrea Stieger; David Stenger; Claudia Scheuer; Jörg H Holstein; Tim Pohlemann; Michael D Menger; Tina Histing Journal: J Orthop Res Date: 2015-04-10 Impact factor: 3.494