Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet-derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 mg) and high (75 ug) doses of recombinant human PDGF-BB (rhPDGF-BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle-treated animals. rhPDGF-BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF-BB treatment significantly increased callus peak torque values (p < 0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF-BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF-BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF-BB may be a new therapeutic approach to treat diabetes-impaired fracture healing. ß

Local insulin delivery has been shown to improve osseous healing in diabetic animals. The purpose of this study was to quantify the effects of local intramedullary delivery of saline or Ultralente insulin (UL) on various fracture healing parameters using an in vivo non-diabetic BB Wistar rat model. Quantitation of local insulin levels showed a rapid release of insulin from the fractured femora, demonstrating complete release at 2 days. RT-PCR analysis revealed that the expression of early osteogenic markers (Col1a2, osteopontin) was significantly enhanced with UL treatment when compared with saline controls (p < 0.05). Significant differences in VEGF þ cells and vascularity were evident between the treatment and control groups at day 7 (p < 0.05). At day 21, histomorphometric analysis demonstrated a significant increase in percent mineralized tissue in the UL-treated animals compared with controls (p < 0.05), particularly within the subperiosteal region of the fracture callus. Mechanical testing at 4 weeks showed significantly greater mechanical strength for UL-treated animals (p < 0.05), but healing in control animals caught up at 6 weeks post-fracture. These results suggest that the primary osteogenic effect of UL during the early stages of fracture healing (1-3 weeks) is through an increase in osteogenic gene expression, subperiosteal angiogenesis, and mineralized tissue formation. ß

A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment. The effect of insulin on diabetic fracture healing has been well documented.1-3 Diabetes leads to reduced cellular proliferation in the early callus, reduced collagen synthesis and content compared to non-diabetic control animals, and reduced biomechanical properties of the healing fracture.1 Administration of systemic insulin to regulate blood glucose within normal levels ameliorates impaired fracture healing in an insulin-dependent diabetic rat model.2 Remarkably though, local insulin treatment at the fracture site in insulin-dependent diabetic rats that were maintained in a severe hyperglycemic state also ameliorates impaired fracture healing associated with diabetes.1,2 Local insulin therapy improved fracture site cell proliferation, cartilage formation, new bone content, and callus strength in hyperglycemic, insulin-dependent, diabetic rats. 1,4The experiments performed in diabetic animals indicate that insulin acts to positively regulate fracture healing at the systemic and local levels. Use of insulin to augment fracture healing or other bone regeneration processes in normal animal models of bone regeneration has not been investigated. Elevating systemic insulin levels would cause hypoglycemia in normal mammals and thus is not a therapeutic option. However, local application of insulin to a fracture site that would provide locally high yet systemically near normal insulin levels could be a therapeutic strategy to enhance fracture healing.The effects of local insulin therapy on femur fracture healing were measured using a non-diabetic rat model. We hypothesize that in a dose dependent manner, local insulin com...

BackgroundStalk lodging is a serious challenge in the production of maize and sorghum. A comprehensive understanding of lodging will likely require accurate characterizations of the mechanical properties of such plants. One of the most important mechanical properties for structural analysis of bending is the modulus of elasticity. The purpose of this study was to measure the modulus of elasticity of dry, mature maize rind tissues using three different loading modes (bending, compression and tensile), and to determine the accuracy and reliability of each test method.ResultsThe three testing modes produced comparable elastic modulus values. For the sample in this study, modulus values ranged between 6 and 16 GPa. All three testing modes exhibited relatively favorable repeatability (i.e. test-to-test variation of < 5%). Modulus values of internodal specimens were significantly higher than specimens consisting of both nodal and internodal tissues, indicating spatial variation in the modulus of elasticity between the nodal and internodal regions.ConclusionsBending tests were found to be the least labor intensive method and also demonstrated the best test-to-test repeatability. This test provides a single aggregate stiffness value for an entire stalk. Compression tests were able to determine more localized (i.e., spatially dependent) modulus of elasticity values, but required additional sample preparation and test time. Finally, tensile tests provided the most focused measurements of the modulus of elasticity, but required the longest sample preparation time.

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Clearly, although DM has a known impact on osseous healing, its negative effects are ameliorated with the application of the rhBMP-2-collagen carrier and demonstrates the potential clinical role of this adjunct in the clinical arena.

BackgroundThe compressional modulus of elasticity is an important mechanical property for understanding stalk lodging, but this property is rarely available for thin-walled plant stems such as maize and sorghum because excised tissue samples from these plants are highly susceptible to buckling. The purpose of this study was to develop a testing protocol that provides accurate and reliable measurements of the compressive modulus of elasticity of the rind of pith-filled plant stems. The general approach was to relying upon standard methods and practices as much as possible, while developing new techniques as necessary.ResultsTwo methods were developed for measuring the compressional modulus of elasticity of pith-filled node–node specimens. Both methods had an average repeatability of ± 4%. The use of natural plant morphology and architecture was used to avoid buckling failure. Both methods relied up on spherical compression platens to accommodate inaccuracies in sample preparation. The effect of sample position within the test fixture was quantified to ensure that sample placement did not introduce systematic errors.ConclusionsReliable measurements of the compressive modulus of elasticity of pith-filled plant stems can be performed using the testing protocols presented in this study. Recommendations for future studies were also provided.

Allograft (Allo) incorporation in the presence of a systemic disease like diabetes mellitus (DM) is becoming a major issue in the orthopedic community. Mesenchymal stem cells (MSC) are multipotent stem cells that may be derived from adult, whole bone marrow and have been shown to induce bone formation in segmental defects when combined with the appropriate carrier/scaffold. The objectives of this study were to analyze the effect of DM upon Allo incorporation in a segmental rat femoral defect and to also investigate MSC augmentation of Allo incorporation. Segmental (5 mm) femoral defects were created in non-DM and DM rats and treated with Allo containing demineralized bone matrix (DBM) or DBM with MSC augmentation. Histological scoring at 4 weeks demonstrated less mature bone in the DM/DBM group compared to its non-DM counterpart (p < 0.001). However, there was significantly more mature bone in the DM/MSC group when compared to the DM/DBM group at both 4 and 8 weeks (p < 0.001 and p ¼ 0.004). Furthermore, significantly more bone formation was observed in the DM/MSC group compared to the DM/DBM group at the 4-week time point (p < 0.001). The results of this study suggest that MSC are a potential adjunct for bone regeneration when implanted in an orthotopic site in the presence of DM. ß