Das Hüftgelenk ist das Paradebeispiel für ein knochengeführtes Gelenk, welches hohen Belastungen selbst bei alltäglichen Tätigkeiten ausgesetzt ist. Der Aufbau und die Struktur mit Bändern und Hilfsstrukturen ist maßgeblich durch seine Funktion bedingt. Eine grundlegende Kenntnis der funktionellen Anatomie sowie der Biomechanik ist die Voraussetzung für das Verständnis der mechanischen Aspekte, welche eine Rolle für die Ausbildung einer Arthrose oder eines Impingement bilden.

Fracture leads to blood vessel rupture inside the bone and in the surrounding soft tissue as well as damage to cells and tissue, which together promotes the initiation of the inflammatory cascade. The acute inflammatory response occurs over the first days after fracture and is thought to initiate the repair cascade by stimulating angiogenesis, attracting and promoting the differentiation of mesenchymal stem cells and enhancing extracellular matrix synthesis. The hematoma forms a blood clot that differentiates into a granulation tissue. The most important cell types involved in bone healing (mesenchymal stem cells, osteoblasts, osteoclasts, fibroblasts and chondrocytes) create tissues like mesenchymal tissue, bone, cartilage and connective tissue. In diaphyseal fractures, the repair phase begins with intramembranous bone formation at the periosteum some distance from the fracture, which drives callus formation. The callus expanse and progresses in diameter and direction to the fracture, which it finally bridges and stabilizes. Cancellous bone in metaphyseal areas appears to heal with no or very limited callus formation but rather by a direct bone formation on existing trabeculae. Following bony bridging, the bone remodeling phase occurs that finally leads to a normal bone structure.

The first tissue differentiation hypotheses were based on the observation that mesenchymal tissue that was stretched could develop into intramembranous bone, whereas mesenchymal tissue under hydrostatic pressure led to endochondral ossification. Later, this observation was developed to a quantitative tissue differentiation hypothesis. Whereas these hypotheses are based on elastic, solid and isotropic material properties, others are based on biphasic material consisting of a fluid and a solid phase. Depending on the tissue differentiation hypothesis used, the mechanical stimulus can be strain energy density, distortional strain, dilatational strain, fluid flow or combinations of these. The chapter focuses on a method using the fuzzy logic method. Using this model, it was finally possible to define optimal axial and shear stiffness values for fracture fixations to obtain a rapid bone healing. The optimal stability was found to be an axial stiffness of between 1000 and 2500 N/mm and a shear stiffness larger than 300 N/mm. Larger diameter intramedullary nails fulfilled that criteria better than unreamed titanium nails with a small diameter and flexible external fixators. Conventional compression plates and interlocking plates often have an extremely high axial stiffness that suppresses the bone healing. To improve the fixation stiffness, several technical and surgical changes are proposed.

There are several approaches for the biomechanical treatment of delayed unions or non-unions, including different methods of externally applied mechanical and physical signals. Five major methods are currently used: cyclic application of interfragmentary movements (IFM), low-magnitude high-frequency vibration (LMHFV), low-intensity pulsed ultrasound (LIPUS), low energy extracorporeal shockwave therapy (ESWT) and surgical dynamization of fractures. LIPUS and dynamization are clinically established methods, whereas ESWT is clinically seldom applied. LIPUS studies showed for non-operatively treated fractures significantly shorter healing times, but this effect could not be demonstrated for fractures treated by intramedullary nailing. Cyclically IFM at external fixators was previously and successfully applied and could significantly reduce the fracture healing time. Some studies showed 50–70% better healing for non-unions treated by ESWT, but the quality of the studies was poor and this needs further investigation. Dynamization can be performed by various techniques. Dynamization by telescoping can accelerate bone healing, while dynamization by destabilization of the fracture fixation in the late healing phase can reduce the time to full weight bearing. Extremely rigid fixations can benefit from an early temporal, dynamization. When the fracture fixation was primarily very flexible, an alteration to a stable fixation should be performed as early as possible.

The original version of this chapter was inadvertently published with incorrect Figure 4.6c, which has been corrected.

A knowledge of some specific methods is important when fracture healing experiments are planned, performed and analyzed. In addition to general guidelines for experimental research, there are specific biomechanical and histomorphological methods. Besides large animal models (sheep, dogs and rabbits) that have been used successfully for a considerable time, the use of small animal models (rats and mice) has become more popular because of lower costs and the possibility to investigate the molecular processes during bone healing. The different physiological loading and bone healing of various animals is described and advantages and restrictions of these models are discussed. The creation of a standardized fracture model is limited to small animals under specific conditions, whereas for large animals, the standardized osteotomy is the method of choice. Loading of the fractured bone model can be by unrestricted or restricted walking or by externally applied forces that create a certain interfragmentary movement. Methods to apply and measure forces and interfragmentary movements are described. Various methods to measure the fracture healing outcome like micro-computed tomography stiffness and strength of healed bones, histomorphological methods to determine the various tissues in the fracture healing zone and methods to determine the structure and amount of blood vessels are described.

The most significant predictors of reoperation following operative management of fractures are the presence of a third degree open fracture, remaining fracture gaps and a transverse fracture. However clinical studies provide no information regarding the involvement of various soft tissues or how the mechanical environment affects revascularisation and bone healing. Here the results of experimental and numerical mechano-biological studies on fracture healing are summarized to provide guidance toward clinical treatment of fractures. In experimental studies, isolated muscle crush appeared to only temporarily impair fracture healing, with no significant effect to the final bone healing, whereas a more severe muscle trauma significantly reduced callus formation and biomechanical properties of the healed bones. An intraoperative trauma can furthermore impede vascularization. Surgical removal of the haematoma or periosteum disturbs fracture healing. While reaming for intramedullary nailing reduced blood flow in the bone during the early phase of bone healing, it did not affect the stiffness or strength of the final bone healing. The optimal conditions for rapid vascularization and bone healing result from fracture fixation that minimizes shearing movements in the healing zone while allowing moderate compressive movements. Bone healing is increasingly delayed with increasing fracture gap size and critical-size defects do not heal sufficiently independent of the mechanical environment. The stiffness of fracture fixation systems like nails and external fixators applied in clinical treatments frequently display a too low stiffness, whereas plate systems often cause a too stiff fixation that suppresses bone healing.

The cyclic axial dynamisation of a stabilised fracture is intended to promote callus formation and bone healing. Most studies focused on biomechanical properties or the quantity of new bone formation. Far less is known about the quality of newly formed callus tissues, such as tissue distribution and arrangement within the callus. The aim of this current study was to investigate the effect of cyclic, axial dynamisation on the quantity and quality of callus in an established delayed fracture healing model. In 41 sheep transverse osteotomies with a gap size of 3 mm were stabilised with a unilateral external fixator. In 32 of these, fracture ends were axially stimulated with displacement amplitudes of 0.8 mm, 0.4 mm, 0.2 mm, or 0.0 mm, respectively, for six weeks. In the remaining 9 sheep of the control group, an additional external fixator was mounted to achieve almost total rigidity. Animal material originating from a past animal experiment was reanalysed in this study. Histological thin-ground sections were histomorphometrically analysed regarding the histological structure and composition of the defect region. A slight tendency towards an increase in size of total callus area, area of new bone (nB.Ar), and cartilage (Cg.Ar) was detected with increasing displacement amplitudes compared to the control group. At the anterior callus side nB.Ar and Cg.Ar were significantly larger than at the posterior side in all groups independent of treatment. Regarding the quality of callus, areas of very compact bone were predominant in the treatment groups whereas in the control group a slight shift to more porous bone was observed. No difference of callus compactness was observed between the anterior and the posterior side. The established method to assess the local compactness of callus areas is a useful tool to quantitatively determine the spatial distribution of new bone tissue within the callus. The application of this method in combination with biomechanical testing might reveal interesting relations between tissue distribution and bone strength that, with traditional histomorphometry, cannot be identified.

Sufficient vascularization of the fracture-healing zone is a prerequisite for undisturbed bone healing. One important factor affecting the vascularization is the interfragmentary movement in the fracture-healing zone. Many studies have demonstrated that stable fixation with predominatly moderate interfragmentary compression movement can stimulate vascularization and the healing process whereas unstable fracture fixation delays the vascularization and bone healing process. Instability of fracture fixation, in particular large shearing interfragmentary movement, can cause delayed healing or non-unions. We hypothesize that the direction of interfragmentary movement affects vascularization in the fracture-healing zone. Cyclic compressive strain stimulates greater vessel formation than tensile or shearing strain. This is due to differences in the local mechanical environment which are not delineated by the direction-independent characterization of interfragmentary movement typically reported. We propose that new vessel formations buckle under compressive loading without significant load transfer across endothelial cell junctions while both tensile and shearing deformations result in disruptive loads despite a biochemically angiogenic environment. From a clinical perspective, this means that the optimal conditions for rapid vascularization result from fracture fixation that minimizes cyclic tensile and shearing movements in the healing zone while allowing moderate compressive movements

Callus distraction is sometimes associated with a delay in the maturation process and serious complications. It is believed that these complications are often caused by instability of the bone segment fixation. Typical fixation devices, such as ring-fixators, show significant deformations in all directions under external loading and muscle forces. This leads to axial compression and tension as well as shear movements in the healing area. Herein we investigated the hypothesis that the direction of interfragmentary movement after callus distraction affects the bone formation and revascularization during the maturation process. Two custom fixator systems were designed to apply a protocol of lateral callus distraction and subsequent cyclic stimulation of the regenerate tissue. One fixator system was used to apply either compressive or tensile stimulation while the other was used to apply shearing stimulation. The fixators were applied to the tibial surface of the right hind leg of sheep specimens. During lateral callus distraction, a titanium plate was elevated by 0.275 mm perpendicular to the long axis of the bone twice daily, resulting in a 5.5 mm gap at the end of the ten-day distraction phase. Following a seven-day consolidation phase, the regenerate in the gap between tibial cortex and titanium plate was stimulated once daily by cyclic movement for 120 cycles. The stimulation was applied for 18 days with amplitudes of 0.6 mm in compression (Group C) or tension (Group T), or a 1.0 mm shear amplitude (Group S). Seven weeks postoperatively the specimens were analyzed for quantity of bone formation, the presence of cartilage and fibrous tissue, and blood vessel density. There was a significantly higher blood vessel density (4.6 ± 1.6%) in Group C than in Group T (1.2 ± 0.4%) or Group S (1.0 ± 0.5%) (p < 0.01). The amount of bone was significantly higher in Group C (25.6% ± 13.0%) than in Group T (13.5 ± 4.9%) (p < 0.05). Group S showed a similar amount of bone (14.0 ± 10.7%) to Group T. The results show that bone formation and revascularization are dependent on the direction of interfragmentary movement and that the cyclic compression best stimulates the healing process.

Multiple studies have sought to characterize the mechanical behavior of callus tissue in vivo during distraction osteogenesis. The aims of such studies are to understand the mechanobiology of distraction and elucidate the complex viscoelasticity and evolution of the tissue. The former objective has direct clinical relevance to surgical technique and process control while the latter is necessary for the calibration and validation of the predictive healing models. Such models seek to reduce the researcher's dependence on animal studies and prospectively allow improved surgical planning. To date, no study has been capable of controlling the mechanical conditions sufficiently enough to decouple the distraction process from the secondary mechanical stimulation associated with the finite stiffness of the fixation constructs employed. It is the goal of this work to understand the mechanobiology of pure distraction as well as characterize viscoelastic tissue behavior under precisely defined mechanical conditions. This is achieved using a novel lateral distraction model. The structural integrity of the bone is maintained, allowing the collection of force relaxation data due to a stepwise distraction process without the superimposed influence of secondary mechanical stimulation. The average instantaneous modulus increases from approximately 2 kPa to approximately 1100 kPa while the equilibrium modulus increases from approximately 0 kPa to 200 kPa over the distraction period.

The mechanical environment is a primary factor in the success of distraction osteogenesis. It is known that the interfragmentary movement during the distraction and maturation phase effects the callus formation. In addition to cyclic compression, other movements like shear and bending influence the bone formation process as shown in previous callus distraction studies. Reports of cartilage presence and endochondral ossification in the regenerative zone have been associated with a lack of fixation stability and delayed healing. So far the effects of the direction of interfragmentary movements could not be studied separately. By means of a unique lateral callus distraction model, we investigated the effects of small (0.1 mm) and moderate (0.6 mm), purely axial compression on ossification during callus maturation in sheep. A distraction device incorporating a mobile titanium plate was mounted on the tibia. Following lateral callus distraction, electromechanically controlled movements allowed purely axial cyclic compression of the tissue regenerate. Seven weeks post-operatively, the tissue regenerates were investigated using μCT, histology and immunohistochemistry. The larger amplitude significantly increased bone formation (Fractional bone volume: 19.4% vs. 5.2%, p = 0.03; trabecular thickness: 0.1 mm vs. 0.06 mm, p = 0.006; mean spicule height: 2.6 mm vs. 1.1 mm, p = 0.02) however, no endochondral ossification occurred. The elimination of shear movement, unimpaired neovascularization as well as the tensile strain stimuli during the distraction phase suppressing chondrogenic differentiation may all contribute to the absence of cartilage. In clinical application of distraction osteogenesis, moderate axial interfragmentary movement augments intramembranous ossification provided shear strain is minimized.

Secondary fracture healing processes are strongly influenced by interfragmentary motion. Shear movement is assumed to be more critical than axial movement, however experimental results are controversial. Numerical fracture healing models allow to simulate the fracture healing process with variation of single input parameters and under comparable normalized mechanical conditions. Therefore, a direct comparison of different in vivo scenarios is possible. The aim of this study was to simulate fracture healing under several axial and shear movement scenarios and compare their respective time to heal. We hypothesize that shear movement is always more critical than axial loading. For the presented study, we used a corroborated numerical model for fracture healing in sheep. Numerous variations of the movement amplitude, the fracture gap size and the musculoskeletal loads were simulated for comparable axial compressive and shear load cases. In all simulated cases, axial compressive load had less inhibitory influe...

Distraction osteogenesis is an effective method for generating large amounts of bone in situ for treating pathologies such as large bone defects or skeletal malformations, for instance leg-length discrepancies. While an optimized distraction procedure might have the potential to reduce the rate of complications significantly, our knowledge of the underlying mechanobiological processes is still insufficient for systematic optimization of treatment parameters such as distraction rate or fixation stiffness. We present a novel numerical model of lateral distraction osteogenesis, based on a mechanically well-controlled in vivo experiment. This model extends an existing numerical model of callus healing with viscoplastic material properties for describing stress relaxation and stimuli history-dependent tissue differentiation, incorporating delay and memory effects. A reformulation of appositional growth based non-local biological stimuli in terms of spatial convolution as well as remeshing and solution-mapping procedures allow the model to cope with severe mesh distortions associated with large plastic deformations. With these enhancements, our model is capable of replicating the in vivo observations for lateral distraction osteogenesis in sheep using the same differentiation rules and the same set of parameters that successfully describes callus healing in sheep, indicating that tissue differentiation hypotheses originally developed for fracture healing scenarios might indeed be applicable to distraction as well. The response of the model to modified distraction parameters corresponds to existing studies, although the currently available data is insufficient for rigorous validation. As such, this study provides a first step towards developing models that can serve as tools for identifying both interesting research questions and, eventually, even optimizing clinical procedures once better data for calibration and validation becomes available.

Background Distraction osteogenesis is a procedure widely used for the correction of large bone defects. However, a high complication rate persists, likely due to insufficient stability during maturation. Numerical fracture healing models predict bone regeneration under different mechanical conditions allowing fixation stiffness optimization. However, most models apply a linear elastic material law inappropriate for the transient stresses/strains present during limb lengthening or segment transport. They are also often validated using in vivo osteotomy models lacking precise mechanical regulation due to the unavoidable stimulation of secondary interfragmentary motion during ambulation under finitely stiff fixation. Therefore, in order to create a robust numerical model of distraction osteogenesis, it is necessary to both characterize the new tissue’s viscoelasticity during distraction and determine the influence of strictly isolated stimulation in each loading mode (tension, compression, and shear) to account for potential differences in mechanical and histological response. Aim Two electromechanical fixators with integrated load cells were designed to precisely perform and monitor in vivo lateral distraction and isolated stimulation in sheep tibiae using a mobile, hydroxyapatite-coated titanium plate. The novel surgical procedure circumvents osteotomy, eliminating the undesirable and unquantifiable mechanical stimulation during ambulation. Methods After a 10-day post-surgery latency period, two 0.275 mm distraction steps were performed daily for 10 days. The load cell collected data before, during, and after each distraction step and was terminated after no less than one minute from the time of distraction. A 7-day consolidation period separated the distraction phase and 18-day stimulation phase. Stimulation was carried out in isolated tension, compression, or shear while recording force/time data. Each stimulation session consisted of 120 cycles with a magnitude of either 0.1 mm or 0.6 mm in the tension and compression groups and 1.0 mm in the shear group. The animals were euthanized after a 3-day holding period following stimulation. Results Our initial results show that the tissue progressively stiffens and maintains an increasingly large residual traction. The force curves during compressive stimulation show a progressive drift from compression toward tension. We hypothesize that this behavior may be due to the preferential flow of fluid outward from the tissue and a greater resistance to reabsorption during the plate’s return to the starting position.

Rat models are widely used in preclinical studies investigating fracture healing. The interfragmentary movement at a fracture site is critical to the course of healing and therefore demands definition in order to aptly interpret the experimental results. Estimation of this movement requires knowledge of the fixation stiffness and loading. The characteristic loading for the rat femur has been estimated, but the stiffness of fixation used in rat studies has yet to be fully described. This study aimed to determine the 6 degree of freedom stiffness of four commonly used implants, two external fixators (RatExFix and UlmExFix), a locking plate, and a locking intramedullary nail, in all degrees of freedom and estimate the interfragmentary movement under specific physiological loads. The external fixator systems allow the greatest movement. Mounted 45° anterolateral on the femur, the RatExFix allows an average of 0.88 mm of motion in each anatomic direction while the stiffer UlmExFix allows about 0.6 mm of motion. The nail is far stiffer than the other implants investigated while the plate allows movement of an intermediate magnitude. Both the nail and plate demonstrate higher axial than shear stiffness. The relatively large standard deviations in external fixator shear motion imply strong dependence on bone axis alignment across the gap and the precise orientation of the specimen relative to the loading. The smaller standard deviation associated with the nail and plate results from improved alignment and minimization of the influence of rotational positioning of the specimen due to the reduced implant eccentricity relative to the specimen axis. These results show that the interfragmentary movement is complex and varies significantly between fixation devices but establishes a baseline for the evaluation of the results of different studies.

Introduction Previously, it was found that fracture healing is impaired by blunt chest trauma and an additional soft-tissue trauma. The mechanisms leading to this disturbance are largely unknown. Here, we investigated the effect of thoracic and soft-tissue trauma on blood flow of the injured lower leg and on tissue differentiation and callus formation during fracture healing.Materials and methods Male Wistar rats received either a mid-shaft fracture of the tibia alone (group A), an additional chest trauma (group B), or additional chest and soft-tissue traumas (group C). Peripheral blood flow was determined by Laser Doppler Flowmetry before and after the injury, and on observation days 1, 3, 7, 14, and 28. Quantitative histological analysis was performed to assess callus size and composition.Results All groups displayed an initial decrease in blood flow during the first 3 days post-trauma. A recovery of the blood flow that even exceeded preoperative levels occurred in group A and later and to a lesser degree in group B, but not in group C. The amount of callus formation decreased with increasing trauma load. More cartilage was formed after 7 days in groups B and C than in group A. At later healing time points, callus composition did not differ significantly.Conclusions An increasing injury burden causes a decreasing blood supply capacity and revascularization, and leads to impaired callus formation and an increasing delay in bone healing.

Background and purpose - Constant fixator stiffness for the duration of healing may not provide suitable mechanical conditions for all stages of bone repair. We therefore investigated the influence of stiffening fixation on callus stiffness and morphology in a rat diaphyseal osteotomy model to determine whether healing time was shortened and callus stiffness increased through modulation of fixation from flexible to stiff. Material and methods - An external unilateral fixator was applied to the osteotomized femur and stiffened by decreasing the offset of the inner fixator bar at 3, 7, 14, and 21 days after operation. After 5 weeks, the rats were killed and healing was evaluated with mechanical, histological, and microcomputed tomography methods. Constant fixation stiffness control groups with either stiff or flexible fixation were included for comparison. Results - The callus stiffness of the stiff group and all 4 experimental groups was greater than in the flexible group. The callus of the flexible group was larger but contained a higher proportion of unmineralized tissue and cartilage. The stiff and modulated groups (3, 7, 14, and 21 days) all showed bony bridging at 5 weeks, as well as signs of callus remodeling. Stiffening fixation at 7 and 14 days after osteotomy produced the highest degree of callus bridging. Bone mineral density in the fracture gap was highest in animals in which the fixation was stiffened after 14 days. Interpretation - The predicted benefit of a large robust callus formed through early flexible fixation could not be shown, but the benefits of stabilizing a flexible construct to achieve timely healing were demonstrated at all time points.

For ex vivo measurements of fracture callus stiffness in small animals, different test methods, such as torsion or bending tests, are established. Each method provides advantages and disadvantages, and it is still debated which of those is most sensitive to experimental conditions (i.e. specimen alignment, directional dependency, asymmetric behavior). The aim of this study was to experimentally compare six different testing methods regarding their robustness against experimental errors. Therefore, standardized specimens were created by selective laser sintering (SLS), mimicking size, directional behavior, and embedding variations of respective rat long bone specimens. For the latter, five different geometries were created which show shifted or tilted specimen alignments. The mechanical tests included three-point bending, four-point bending, cantilever bending, axial compression, constrained torsion, and unconstrained torsion. All three different bending tests showed the same principal behavior. They were highly dependent on the rotational direction of the maximum fracture callus expansion relative to the loading direction (creating experimental errors of more than 60%), however small angular deviations (<15°) were negligible. Differences in the experimental results between the bending tests originate in their respective location of maximal bending moment induction. Compared to four-point bending, three-point bending is easier to apply on small rat and mouse bones under realistic testing conditions and yields robust measurements, provided low variation of the callus shape among the tested specimens. Axial compressive testing was highly sensitive to embedding variations, and therefore cannot be recommended. Although it is experimentally difficult to realize, unconstrained torsion testing was found to be the most robust method, since it was independent of both rotational alignment and embedding uncertainties. Constrained torsional testing showed small errors (up to 16.8%, compared to corresponding alignment under unconstrained torsion) due to a parallel offset between the specimens' axis of gravity and the torsional axis of rotation.