Browsing by Author "Bemenderfer, Thomas B."

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    A Review of Mouse Critical Size Defect Models in Weight Bearing Bones
    (Elsevier, 2013) Harris, Jonathan S.; Bemenderfer, Thomas B.; Wessel, Alexander R.; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
    Current and future advances in orthopedic treatment are aimed at altering biological interactions to enhance bone healing. Currently, several clinical scenarios exist for which there is no definitive treatment, specifically segmental bone loss from high-energy trauma or surgical resection - and it is here that many are aiming to find effective solutions. To test experimental interventions and better understand bone healing, researchers employ critical size defect (CSD) models in animal studies. Here, an overview of CSDs is given that includes the specifications of varying models, a discussion of current scaffold and bone graft designs, and current outcome measures used to determine the extent of bone healing. Many promising graft designs have been discovered along with promising adjunctive treatments, yet a graft that offers biomechanical support while allowing for neovascularization with eventual complete resorption and remodeling remains to be developed. An overview of this important topic is needed to highlight current advances and provide a clear understanding of the ultimate goal in CSD research--develop a graft for clinical use that effectively treats the orthopedic conundrum of segmental bone loss.
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    Thrombopoietic agents enhance bone healing in mice, rats, and pigs
    (Oxford University Press, 2024) Childress, Paul J.; Nielsen, Jeffery J.; Bemenderfer, Thomas B.; Dadwal, Ushashi C.; Chakraborty, Nabarun; Harris, Jonathan S.; Bethel, Monique; Alvarez, Marta B.; Tucker, Aamir; Wessel, Alexander R.; Millikan, Patrick D.; Wilhite, Jonathan H.; Engle, Andrew; Brinker, Alexander; Rytlewski, Jeffrey D.; Scofield, David C.; Griffin, Kaitlyn S.; Shelley, W. Christopher; Manikowski, Kelli J.; Jackson, Krista L.; Miller, Stacy-Ann; Cheng, Ying-Hua; Ghosh, Joydeep; Mulcrone, Patrick L.; Srour, Edward F.; Yoder, Mervin C.; Natoli, Roman M.; Shively, Karl D.; Gautam, Aarti; Hammamieh, Rasha; Low, Stewart A.; Low, Philip S.; McKinley, Todd O.; Anglen, Jeffrey O.; Lowery, Jonathan W.; Chu, Tien-Min G.; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
    Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, have renewed interest in investigating alternatives that provide safer, yet effective bone regeneration. Here we demonstrate the robust bone healing capabilities of the main megakaryocyte (MK) growth factor, thrombopoietin (TPO), and second-generation TPO agents using multiple animal models, including mice, rats, and pigs. This bone healing activity is shown in two fracture models (critical-sized defect [CSD] and closed fracture) and with local or systemic administration. Our transcriptomic analyses, cellular studies, and protein arrays demonstrate that TPO enhances multiple cellular processes important to fracture healing, particularly angiogenesis, which is required for bone union. Finally, the therapeutic potential of thrombopoietic agents is high since they are used in the clinic for other indications (eg, thrombocytopenia) with established safety profiles and act upon a narrowly defined population of cells.