Reduced Bending Stiffness Research Articles

Functional significance of lamellar architecture in marine sponge fibers: Conditions for when splitting a cylindrical tube into an assembly of tubes will decrease its bending stiffness

Numerous ingenious engineering designs and devices have been the product of bio-inspiration. Bone, nacre, and other such stiff structural biological materials (SSBMs) are composites that contain mineral and organic materials interlaid together in layers. In nacre, this lamellar architecture is known to contribute to its fracture toughness, and has been investigated with the goal of discovering new engineering material design principles that can aid the development of synthetic composites that are both strong and tough. The skeletal anchor fibers (spicules) of Euplectella aspergillum (Ea.) also display a lamellar architecture; however, it was recently shown using fracture mechanics experiments and computations that the lamellar structure in them does not significantly contribute to their fracture toughness. An alternate hypothesis—the load carrying capacity (LCC) hypothesis—regarding the lamellar architecture’s functional significance in Ea. spicules is that it enhances the spicule’s strength, rather than its toughness. From an ecology perspective the LCC hypothesis is certainly plausible, since a higher strength would allow the spicules to more firmly anchor Ea. to the sea floor, which would be beneficial to it since it is a filter feeding animal. In this paper we present support for the LCC hypothesis from a solid and structural mechanics perspective, which, compared to the support from ecology, is far harder to identify but equally, if not more, compelling and valid. We found that when the spicule functions in a knotted configuration a reduced bending stiffness benefits its load carrying capacity and that sectioning a cylindrical tube into an assembly of co-axial tubes can reduce the tube’s bending stiffness for a wide class of materials that are consistent with the spicules’ axial symmetry. The mechanics theory developed in this paper has applications beyond providing support for the LCC hypothesis. For example, it makes apparent many design strategies for reducing the bending stiffness of large industrial cables (e.g., undersea optical data transmission cables) while maintaining their tensile strength, which has benefits towards the handling, storage, and transportation of such cables.

A comparison of earthwork designs for railway transition zones

Railway track transitions are zones where there is an abrupt change in the track-ground structure. They are often the location of rapid track deterioration, which means more frequent track maintenance is needed compared to plain line tracks. With the aim of reducing maintenance, modern transition zone designs use tapered stiffness earthwork profiles to minimise train-track dynamics. However, there has been limited comparison regarding the effect of different tapered profiles on dynamic behaviour. Therefore, this paper’s novelty is the investigation of the performance of different earthwork designs in smoothing stiffness transition’s considering different types of improvement and also train speed. To do so, first a 3D finite element track model is developed, with support conditions transitioning from an earth embankment onto a concrete bridge. A dynamic moving train load is simulated using a rigid multi-body approach capable of accounting for train-track interaction. The model is used to study the effect of four earthwork solutions with differing stiffness tapers. For each scenario, two different track structure types (ballast and concrete slab) are considered, along with different magnitudes of ground improvement. Lastly, the effects of train speed are explored. It is found tapered earthwork solutions for ballasted tracks show greater dynamic improvement compared to slabs due to their reduced bending stiffness. Further, the more complex improvement geometries such as double trapezoid shapes offer some additional improvement at locations within 3 m of the bridge. However, when considering such tapered stiffness-based earthwork solutions, additional factors such as constructability must also be considered.

Diclofenac, a NSAID, delays fracture healing in aged mice

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, belong to the most prescribed analgesic medication after traumatic injuries. However, there is accumulating evidence that NSAIDs impair fracture healing. Because bone regeneration in aged patients is subject to significant changes in cell differentiation and proliferation as well as a markedly altered pharmacological action of drugs, we herein analyzed the effects of diclofenac on bone healing in aged mice using a stable closed femoral facture model. Thirty-three mice (male n = 14, female n = 19) received a daily intraperitoneal injection of diclofenac (5 mg/kg body weight). Vehicle-treated mice (n = 29; male n = 13, female n = 16) served as controls. Fractured mice femora were analyzed by means of X-ray, biomechanics, micro computed tomography (μCT), histology and Western blotting. Biomechanical analyses revealed a significantly reduced bending stiffness in diclofenac-treated animals at 5 weeks after fracture when compared to vehicle-treated controls. Moreover, the callus tissue in diclofenac-treated aged animals exhibited a significantly reduced amount of bone tissue and higher amounts of fibrous tissue. Further histological analyses demonstrated less lamellar bone after diclofenac treatment, indicating a delay in callus remodeling. This was associated with a decreased number of osteoclasts and an increased expression of osteoprotegerin (OPG) during the early phase of fracture healing. These findings indicate that diclofenac delays fracture healing in aged mice by affecting osteogenic growth factor expression and bone formation as well as osteoclast activity and callus remodeling.

Closed‐form buckling analysis of unsymmetrically laminated plates

AbstractThe local stability of thin‐walled fibre‐reinforced plastic composite beams can be reduced to individual laminates using discrete plate theory. These individual plates receive a supporting effect from their surrounding structure, which is modelled with rotational restraints. In the present investigation, this buckling problem is described by a closed‐form solution. The energy‐based method works with the Rayleigh quotient and the principle of the stationary value of the elastic potential energy. For the analysis of unsymmetrically laminated plates, the classical laminated plate theory (CLPT) considers both the plate deflection and the in‐plane displacements. The first‐order shear deformation theory (FSDT) and third‐order shear deformation theory (TSDT) additionally describe the cross‐sectional rotations and thus take transverse shear deformations into account. In addition to the direct consideration of the bending‐extension couplings, these have also been investigated using the reduced bending stiffness (RBS) method. The investigation shows the influence of bending‐extension coupling on the stability of compressively loaded unsymmetrically laminated plates. Moreover, it is found that the transverse shear stiffness reduces the critical load at relatively high plate thicknesses. The closed‐form analytical solution and the RBS method show good agreement with finite element analyses. The presented closed‐form analytical methods provide explicit solutions for the critical compressive load of unsymmetric laminates under different boundary conditions. Due to the explicit solution, this method is significantly more computationally efficient than numerical, semi‐analytical or exact methods. The present methods are characterised by a simple applicability as well as a very high computational efficiency and are very suitable for preliminary design as well as optimisation of laminated structures.

Electronic Packaging Enhancement Engineered by Reducing the Bonding Temperature via Modified Cure Cycles.

Semiconductor packaging continues to reduce in thickness following the overall thinning of electronic devices such as smartphones and tablets. As the package becomes thinner, the warpage of the semiconductor package becomes more important due to the reduced bending stiffness and driven by thermal residual stresses and thermal expansion mismatch during the epoxy molding compound (EMC) curing to create the package. To address this packaging reliability issue, in this study, we developed a modified cure cycle that adds a rapid cooling step to the conventional cure cycle (CCC) to enhance the reliability of the EMC molded to a copper substrate (EMC/Cu bi-layer package) by lowering the bonding temperature of the EMC/Cu bi-layer package. Modeling of the package via Timoshenko theory including effective cure shrinkage allowed the rapid cooling step to be quantified and confirmed via experiments. The modified cure cycle resulted in a 26% reduction in residual strain, a 27% reduction in curvature, and a 40% increase in peel strength compared to the CCC, suggesting that this is an effective new method for managing warping effects in such packaged structures.

The stiffness of a reinforced concrete beam with random parameters the cracks formation

The work of a reinforced concrete beam lying on an elastic foundation is considered, the deformation characteristics of which are described by a model with two Vlasov-Pasternak bed coefficients. The bed coefficients are considered as stationary random normally distributed functions of the x coordinate. Strength characteristics of concrete: cube strength and concrete tensile strength are assumed to be random variables with Gaussian probability density distributions. The concentrated forces approximating the columns of the building are applied at regular intervals and are assumed to be random normally distributed values. After the formation of cracks in the sections under concentrated forces in the beam, areas with a reduced bending stiffness are formed, and therefore the stiffness of the beam becomes variable along the length of the beam. The solution of the differential equation of bending of a beam with variable stiffness lying on an elastic foundation is proposed to be sought by a variational method minimizing the functional of the additional energy principle. The deflections of a beam with variable stiffness will be approximated by a function that satisfies the boundary conditions and the equilibrium condition. From the equality of the deflections of a beam with constant equivalent bending stiffness and deflections of a beam with variable bending stiffness due to cracking, the constant equivalent stiffness and its statistical parameters are determined. Knowing the constant equivalent bending stiffness of a concrete beam and using the known solutions of the bending equation of a beam lying on an elastic foundation with random properties, it becomes possible to find the probabilistic parameters of bending moments and shear forces and to determine the probability of the onset of limit states of the beam along the normal and inclined sections.

Adaptive polymer fiber neural device for drug delivery and enlarged illumination angle for neuromodulation

Objective. Optical fiber devices constitute significant tools for the modulation and interrogation of neuronal circuitry in the mid and deep brain regions. The illuminated brain area during neuromodulation has a direct impact on the spatio-temporal properties of the brain activity and depends solely on the material and geometrical characteristics of the optical fibers. In the present work, we developed two different flexible polymer optical fibers (POFs) with integrated microfluidic channels (MFCs) and an ultra-high numerical aperture (UHNA) for enlarging the illumination angle to achieve efficient neuromodulation. Approach. Three distinct thermoplastic polymers: polysulfone, polycarbonate, and fluorinated ethylene propylene were used to fabricate two step-index UHNA POF neural devices using a scalable thermal drawing process. The POFs were characterized in terms of their illumination map as well as their fluid delivery capability in phantom and adult rat brain slices. Main results. A 100-fold reduced bending stiffness of the proposed fiber devices compared to their commercially available counterparts has been found. The integrated MFCs can controllably deliver dye (trypan blue) on-demand over a wide range of injection rates spanning from 10 nl min−1 to 1000 nl min−1. Compared with commercial silica fibers, the proposed UHNA POFs exhibited an increased illumination area by 17% and 21% under 470 and 650 nm wavelength, respectively. In addition, a fluorescent light recording experiment has been conducted to demonstrate the ability of our UHNA POFs to be used as optical waveguides in fiber photometry. Significance. Our results overcome the current technological limitations of fiber implants that have limited illumination area and we suggest that soft neural fiber devices can be developed using different custom designs for illumination, collection, and photometry applications. We anticipate our work to pave the way towards the development of next-generation functional optical fibers for neuroscience.

La stabilisation hybride pédiculaire protège-t-elle les fixations lombaires postérieures des échecs du segment adjacent ? Analyse par éléments finis et comparaison de différents systèmes

IntroductionInterbody fusion is a very common surgical treatment for degenerative disc diseases. It is necessary to explain the effect of pedicle based hybrid stabilization systems (PBHS) on the lumbar spine, as there is no consensus in the literature about their performance. HypothesisTopping off a fusion with a PBHS may provide some protection against adjacent segment failure. Material and methodsThe biomechanical effect PBHS on fused and adjacent to fusion levels were investigated, including range of motion, bending stiffness, Von Mises stress A 3D Finite Element model of the L2–S1 spine was used and modified to simulate pre and postoperative changes during combined loading. Five models instrumented with different systems [Titanium and PEEK fusion; Dynesys hybrid system; NFlex hybrid stabilization and PEEK topping off fusion] were compared to those of healthy model. ResultsAfter hybrid instrumentation, the L4–L5 level did not lose its motion completely, NFlex hybrid stabilization system maintained 82 % of flexion at the adjacent to fusion level, reduced bending stiffness by 40 % in axial rotation. Dynesys hybrid system represented more restricted motion than NFlex. PEEK topping off fusion system was the most rigid one among all three systems. It increased bending stiffness at the adjacent level and increased the axial motion by 25 %. High risk of rod breakage was computed for PEEK topping off system as 48.8MPa in lateral bending. ConclusionHybrid stabilization can delay adjacent segment failure and compensate lumbar spine mobility. However, it is clear that PBHS need to be further tested before being considered for clinical use. Level of evidenceIII; Well-designed computational non-experimental study.

Is Pedicle-Based Hybrid Stabilization (PBHS) protecting posterior lumbar fixation from adjacent-segment failure? Finite element analysis and comparison of different systems

IntroductionInterbody fusion is a very common surgical treatment for degenerative disc diseases. It is necessary to explain the effect of Pedicle Based Hybrid Stabilization systems (PBHS) on the lumbar spine, as there is no consensus in the literature about their performance. HypothesisTopping off a fusion with a PBHS may provide some protection against adjacent segment failure. Material and methodsThe biomechanical effect PBHS on fused and adjacent to fusion levels were investigated, including range of motion, bending stiffness, Von Mises stress A 3D Finite Element model of the L2-S1 spine was used and modified to simulate pre and postoperative changes during combined loading. Five models instrumented with different systems [Titanium and PEEK fusion; Dynesys hybrid system; NFlex hybrid stabilization and PEEK topping off fusion] were compared to those of healthy model. ResultsAfter hybrid instrumentation, the L4–L5 level did not lose its motion completely, NFlex hybrid stabilization system maintained 82% of flexion at the adjacent to fusion level, reduced bending stiffness by 40% in axial rotation. Dynesys hybrid system represented more restricted motion than NFlex. PEEK topping off fusion system was the most rigid one among all three systems. It increased bending stiffness at the adjacent level and increased the axial motion by 25%. High risk of rod breakage was computed for PEEK topping off system as 48.8MPa in lateral bending. ConclusionHybrid stabilization can delay adjacent segment failure and compensate lumbar spine mobility. However, it is clear that PBHS need to be further tested before being considered for clinical use. Level of evidenceIII; well-designed computational non-experimental study.

Studies on the validity of the reduced bending stiffness method for eccentrically stacked laminates

AbstractThe reduced bending stiffness method is used in the framework of computational models for stringer stiffened panels. Here, the stringer foot is often stacked on top of the skin of the panel and leads to a stacked laminate with extensional bending stiffness coupling. The validity of the reduced bending stiffness method for the mentioned laminate type is investigated and assessed, as only unsymmetrical laminates without eccentricity have been considered in existing literature. In exemplary studies, the influence of the coupling effects is shown, which allows drawing conclusions on the error that is introduced in, e. g. closed‐form analytical approximate solutions for the buckling of stringer stiffened panels.

Pantoprazole impairs fracture healing in aged mice

Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in young adult mice. Because differentiation and proliferation in fracture healing as well as pharmacologic actions of drugs markedly differ in the elderly compared to the young, we herein studied the effect of the PPI pantoprazole on bone healing in aged mice using a murine fracture model. Bone healing was analyzed by biomechanical, histomorphometric, radiological and protein biochemical analyses. The biomechanical analysis revealed a significantly reduced bending stiffness in pantoprazole-treated animals when compared to controls. This was associated with a decreased amount of bone tissue within the callus, a reduced trabecular thickness and a higher amount of fibrous tissue. Furthermore, the number of osteoclasts in pantoprazole-treated animals was significantly increased at 2 weeks and decreased at 5 weeks after fracture, indicating an acceleration of bone turnover. Western blot analysis showed a lower expression of the bone morphogenetic protein-4 (BMP-4), whereas the expression of the pro-angiogenic parameters was higher when compared to controls. Thus, pantoprazole impairs fracture healing in aged mice by affecting angiogenic and osteogenic growth factor expression, osteoclast activity and bone formation.

Enhancing strength and toughness of adhesive joints via micro-structured mechanical interlocking

The potential to improve the mechanical properties of adhesive joints via micro-structured interlocking features is investigated. The micro-structured surfaces were fabricated in polycarbonate via injection moulding from a master template. The specimens were then bonded in an interlocking configuration to form single lap joints and tested to failure in tension. Planar untreated (i.e. un-abraded) and planar roughened (i.e. abraded) samples were also tested to provide benchmarks. Compared to the planar roughened case, results show that micro-structuring the interface can yield up to a 95.9% increase in strength and up to 162% increase in work to failure. Increases in strength and work to failure beyond the planar roughened level are attributed to mechanical interlocking of features. As deformation proceeds, progressive bending of each pair of interlocking features develops an increasing resistive load which allows the total load to significantly exceed that of the planar roughened case. Work to failure is increased via a combination of increased maximum force, increased displacement enabled by microfeature bending and a more torturous crack path. Low clearances between interlocking features were found to be favourable for mechanical properties owing to reduced bending stiffness of the repeating periodic unit at the interface.

Stress magnification factor for angular misalignment between plates with welding-induced curvature

The construction of lightweight structures poses new design challenges as a result of the different mechanics of deformation experienced by thinner-plated structures. Because of a reduced bending stiffness, thin plates are particularly sensitive to welding-induced distortions, which include a curvature, in addition to the axial and global angular misalignment observed on thick plates. The curvature shape and amplitude determine a local angular misalignment at the welded joint, which causes non-negligible secondary bending effects. Therefore, the commonly used stress magnification factors km solution for flat plates need a further development to include the curvature effect. This study proposes new analytical formulations, which extend the applicability of the existing solutions to the assessment of the structural stress of a curved thin plate under an axial load. The improved formulations are consistent with the geometrical non-linear finite element analysis under compression (up to sim 80% of the buckling limit) and tension (up to the yield strength). A sensitivity analysis is presented in order to show the dominant role of the curvature effect in the estimation of the km factor. Regardless of the load applied, the presence of the curvature causes a flat plate solution inaccuracy greater than 10% when the local angular misalignment is more than 1.25 times higher than the global angular misalignment in the case of a thin and slender structure.

Erythropoietin does not improve fracture healing in aged mice.

Fracture healing in the elderly is associated with a declined healing potential caused by multiple factors including a delay of vascularization. Erythropoietin (EPO) has been demonstrated to improve vascularization and fracture healing in adult mice. We, therefore, hypothesized that EPO in aged mice also improves fracture healing. For this purpose, EPO was given daily in a femoral fracture model in aged mice and compared to vehicle-treated controls using radiological, biomechanical, histomorphometric and Western blot techniques. Blood analyses revealed significantly higher concentrations of hemoglobin and a higher hematocrit in EPO-treated animals at 14 and 35 days after fracture. Micro-computed tomography (μCT) indicated that the fraction of bone volume/tissue volume within the callus did not differ between the two groups. However, μCT showed a 3-fold increased tissue mineral density (TMD) in the callus of EPO-treated animals compared to controls. The callus TMD of the EPO-treated animals was also 2-fold higher when compared to the TMD of the unfractured contralateral femur. Interestingly, biomechanical analyses revealed a reduced bending stiffness in femurs of EPO-treated animals at day 35. The histomorphometrically analyzed callus size and callus composition did not show significant differences between the study groups. However, Western blot analyses exhibited an increased expression of osteoprotegerin (OPG), but in particular of receptor activator of NF-κB ligand (RANKL) in the callus of the EPO-treated animals. Further histological analyses of the callus tissue showed that this was associated with an increased number of newly formed blood vessels and a higher number of tartrate-resistant acid phosphatase (TRAP)+ cells. Conclusion: In fracture healing of aged mice EPO treatment increases callus TMD as well as OPG and RANKL expression, indicating an accelerated bone turnover when compared to controls. However, EPO does not improve fracture healing in aged mice. The process of fracture healing may be altered by EPO due to a deterioration of the microcirculation caused by the worsened rheological properties of the blood and due to an increased bone fragility caused by the accelerated bone turnover. Thus, EPO may not be used to improve fracture healing in the elderly.

Effects of locally applied adipose tissue-derived microvascular fragments by thermoresponsive hydrogel on bone healing

Insufficient vascularization is a major cause for the development of non-unions. To overcome this problem, adipose tissue-derived microvascular fragments (MVF) may serve as vascularization units. However, their application into bone defects needs a carrier system. Herein, we analyzed whether this is achieved by a thermoresponsive hydrogel (TRH). MVF were isolated from CD-1 mice and cultivated after incorporation into TRH, while non-incorporated MVF served as controls. Viability of MVF was assessed immunohistochemically over a 7-day period. Moreover, osteotomies were induced in femurs of CD-1 mice. The osteotomy gaps were filled with MVF-loaded TRH (TRH + MVF), unloaded TRH (TRH) or no material (control). Bone healing was evaluated 14 and 35 days postoperatively. MVF incorporated into TRH exhibited less apoptotic cells and showed a stable vessel morphology compared to controls. Micro-computed tomography revealed a reduced bone volume in TRH + MVF femurs. Histomorphometry showed less bone and more fibrous tissue after 35 days in TRH + MVF femurs compared to controls. Accordingly, TRH + MVF femurs exhibited a lower osseous bridging score and a reduced bending stiffness. Histology and Western blot analysis revealed an increased vascularization and CD31 expression, whereas vascular endothelial growth factor (VEGF) expression was reduced in TRH + MVF femurs. Furthermore, the callus of TRH + MVF femurs showed increased receptor activator of NF-κB ligand expression and higher numbers of osteoclasts. These findings indicate that TRH is an appropriate carrier system for MVF. Application of TRH + MVF increases the vascularization of bone defects. However, this impairs bone healing, most likely due to lower VEGF expression during the early course of bone healing. Statement of significanceIn the present study we analyzed for the first time the in vivo performance of a thermoresponsive hydrogel (TRH) as a delivery system for bioactive microvascular fragments (MVF). We found that TRH represents an appropriate carrier for MVF as vascularization units and maintains their viability. Application of MVF-loaded TRH impaired bone formation in an established murine model of bone healing, although vascularization was improved. This unexpected outcome was most likely due to a reduced VEGF expression in the early phase bone healing.

Lattice flexures: Geometries for stiffness reduction of blade flexures

Reducing the motion-direction stiffness of compliant mechanisms reduces their actuation effort and simplifies associated static balancing mechanisms. This work introduces a flexure type called lattice flexures and evaluates some of their fundamental properties. Lattice flexures have a reduced bending stiffness when compared to traditional rectangular-section blade flexures of similar size. The motion-direction bending stiffness of two lattice flexure types, called X-type and V-type, are analytically derived, corroborated with finite element analysis, and validated with measurements of physical prototypes. The lattice flexure has the potential to reduce the bending stiffness of some compliant mechanisms by 60–80%, as demonstrated in devices manufactured using 3D printing technologies. It is shown that some lattice flexures exhibit a torsional/bending stiffness ratio as much as 1.7 times higher than an equal aspect-ratio blade flexure, and a transverse bending/motion-direction bending stiffness ratio up to 6.5 times higher than an equal aspect-ratio blade flexure.

Sexual Dimorphism and Population Differences in Structural Properties of Barn Swallow (Hirundo rustica) Wing and Tail Feathers.

Sexual selection and aerodynamic forces affecting structural properties of the flight feathers of birds are poorly understood. Here, we compared the structural features of the innermost primary wing feather (P1) and the sexually dimorphic outermost (Ta6) and monomorphic second outermost (Ta5) tail feathers of barn swallows (Hirundo rustica) from a Romanian population to investigate how sexual selection and resistance to aerodynamic forces affect structural differences among these feathers. Furthermore, we compared structural properties of Ta6 of barn swallows from six European populations. Finally, we determined the relationship between feather growth bars width (GBW) and the structural properties of tail feathers. The structure of P1 indicates strong resistance against aerodynamic forces, while the narrow rachis, low vane density and low bending stiffness of tail feathers suggest reduced resistance against airflow. The highly elongated Ta6 is characterized by structural modifications such as large rachis width and increased barbule density in relation to the less elongated Ta5, which can be explained by increased length and/or high aerodynamic forces acting at the leading tail edge. However, these changes in Ta6 structure do not allow for full compensation of elongation, as reflected by the reduced bending stiffness of Ta6. Ta6 elongation in males resulted in feathers with reduced resistance, as shown by the low barb density and reduced bending stiffness compared to females. The inconsistency in sexual dimorphism and in change in quality traits of Ta6 among six European populations shows that multiple factors may contribute to shaping population differences. In general, the difference in quality traits between tail feathers cannot be explained by the GBW of feathers. Our results show that the material and structural properties of wing and tail feathers of barn swallows change as a result of aerodynamic forces and sexual selection, although the result of these changes can be contrasting.

Smart sensing of damage in flexible plates through MEMS

In this work, we present a methodology to monitor the state of damage- or crack-containing flexible plates through low-cost, commercial off-the-shelf MEMS accelerometers. Under quasi-static, time-varying loading conditions we track the evolution of the damaged zone (e.g., the length of an inner crack) accounting for the drift in the compliance of the specimens, measured by means of the magnitude of the load-induced rotation at MEMS position. We then validate this health monitoring methodology, showing that it turns out to be sensitive to the damage and provides results in good accordance with theoretical findings. Next, we propose a technique to optimally deploy the MEMS sensors over the plate. Referring to an isotropic square plate containing damaged zones of reduced bending stiffness, we numerically investigate the sensitivity of the load-induced state (in terms of out-of-plane displacement and rotation of the normal to the mid-plane) to the position of the damaged area, and we adopt a constrained topology optimisation tool to determine the best sensor deployment to efficiently sense the damage.

Complement C3 and C5 Deficiency Affects Fracture Healing

There is increasing evidence that complement may play a role in bone development. Our previous studies demonstrated that the key complement receptor C5aR was strongly expressed in the fracture callus not only by immune cells but also by bone cells and chondroblasts, indicating a function in bone repair. To further elucidate the role of complement in bone healing, this study investigated fracture healing in mice in the absence of the key complement molecules C3 and C5. C3-/- and C5-/- as well as the corresponding wildtype mice received a standardized femur osteotomy, which was stabilized using an external fixator. Fracture healing was investigated after 7 and 21 days using histological, micro-computed tomography and biomechanical measurements. In the early phase of fracture healing, reduced callus area (C3-/-: -25%, p=0.02; C5-/-: -20% p=0.052) and newly formed bone (C3-/-: -38%, p=0.01; C5-/-: -52%, p=0.009) was found in both C3- and C5-deficient mice. After 21 days, healing was successful in the absence of C3, whereas in C5-deficient mice fracture repair was significantly reduced, which was confirmed by a reduced bending stiffness (-45%; p=0.029) and a smaller callus volume (-17%; p=0.039). We further demonstrated that C5a was activated in C3-/- mice, suggesting cleavage via extrinsic pathways. Our results suggest that the activation of the terminal complement cascade in particular may be crucial for successful fracture healing.

Delayed Fracture Healing in Aged Senescence-Accelerated P6 Mice

ABSTRACTBackground: Osteoporosis is characterized by poor bone quality. However, it is still controversially discussed whether osteoporosis compromises fracture healing. Herein, we studied whether the course of healing of a femur fracture is affected by osteoporosis or age. Methods: Using the senescence-accelerated osteoporotic mouse, strain P6 (SAMP6), and a closed femur fracture model, we studied the process of fracture healing in 5- and 10-month-old animals, including biomechanical, histomorphometric, and protein biochemical analysis. Results: In five-month-old osteoporotic SAMP6 mice, bending stiffness, callus size, and callus tissue distribution as well as the concentrations of the bone formation marker osteocalcin and the bone resorption markers tartrate-resistant acid phosphatase form 5b (TRAP) and deoxypyridinoline (DPD) did not differ from that of non-osteoporotic, senescence-resistant, strain 1 (SAMR1) controls. In contrast, femur fractures in 10-month-old SAMP6 mice showed a significantly reduced bending stiffness and an increased callus size compared to fractures in age-matched SAMR1 controls. This indicates a delayed fracture healing in advanced age SAMP6 mice. The delay of fracture healing was associated with higher concentrations of TRAP and DPD. Significant differences in osteocalcin concentrations were not found between SAMP6 animals and SAMR1 controls. Conclusion: In conclusion, the present study indicates that fracture healing in osteoporotic SAMP6 mice is not affected in five-month-old animals, but delayed in animals with an age of 10 months. This is most probably due to the increased osteoclast activity in advanced age SAMP6 animals.