A Biomechanical Evaluation of Auricular Cartilage Autografts in Orbital Floor Defect Repair.

OBJECTIVE: Auricular cartilage is used as a surgical implant in the management of orbital floor fractures. However, no specific parameters exist regarding the use/limitations of this potential graft. In order to determine the mechanical efficacy of adult auricular cartilage grafts, a mechanical model was developed and studied for structural threshold size limits. METHODS: Thirty-seven cadaveric auricular cartilage specimens were tested in a laboratory. A plexiglass baseplate was created with four different sized holes, defined as 1.0×, 1.2×, 1.4×, and 1.6× the mean minor axis of the specimens. Each specimen was used to bridge one hole under increasing loads until mechanical failure. Structural stiffness at three different loading stages, structural failure strength, and percent failure of the entire system for each defect size was calculated. RESULTS: Specimens tested on 1.0×, 1.2×, 1.4× and 1.6× defects demonstrated 0%, 0%, 20%, and 60% system failure rates, respectively. Structural stiffness curves showed a similar trend, with ANOVA demonstrating a significant difference in mechanical properties between defect sizes (p = 0.03). The curve representing 1.6 × defect size demonstrated significantly reduced structural stiffness relative to 1.0×, 1.2×, and 1.4× curves. There was no statistical difference between 1.2× and 1.4× testing sets (p = 0.09). CONCLUSION: A clinically significant biomechanical and functional threshold exists between 1.2×and 1.4× defect sizes. Given a mean minor axis of 2.06 cm, orbital blow-out defects <2.4 cm (1.2 × 2.06 cm) are suitable for auricular cartilage grafts; fractures >2.4 cm may require a more rigid material. Cartilage grafts that allow failure, however, may better protect the globe in subsequent injury.

A multilevel hierarchical finite element model for capillary failure in soft tissue.

Bruising, the result of capillary failure due to trauma, is a common indication of abuse. However, the etiology of capillary failure has yet to be determined as the scale change from tissue to capillary represents several orders of magnitude. As a first step toward determining bruise etiology, we have developed a multilevel hierarchical finite element model (FEM) of a portion of the upper human arm using a commercial finite element tool and a series of three interconnected hierarchical submodels. The third and final submodel contains a portion of the muscle tissue in which a single capillary is embedded. Nonlinear, hyperelastic material properties were applied to skin, adipose, muscle, and capillary wall materials. A pseudostrain energy method was implemented to subtract rigid-body-like motion of the submodel volume experienced in the global model, and was critical for convergence and successful analyses in the submodels. The deformation and hoop stresses in the capillary wall were determined and compared with published capillary failure stress. For the dynamic load applied to the skin of the arm (physiologically simulating a punch), the model predicted that approximately 8% volume fraction of the capillary wall was above the reference capillary failure stress, indicating bruising would likely occur.

Determining bruise etiology in muscle tissue using finite element analysis.

Bruising, the result of capillary failure, is a common physical exam finding due to blunt trauma and, depending on location and severity, a potential indicator of abuse. Despite its clinical relevance, few studies have investigated the etiology of capillary failure. The goal of this study was to determine whether capillaries primarily fail under shear stress or hydraulic-induced tensile stress. An arteriole bifurcating into four capillaries was modeled using ANSYS 14.0 (®) . The capillaries were embedded in muscle tissue and a pressure of 20.4 kPa was applied. Any tensile stress exceeding 8.4 × 10(4)  Pa was considered failure. Results showed that failure occurred directly under the impact zone and where capillaries bifurcated, rather than along the line of greatest shear stress, indicating that internal tensile stress is likely the primary mode of capillary failure in bruising. These results are supported by the concept that bruising can occur via blunt trauma in which no shearing lacerations occur.

Severity of injury and the decision to arrest in cases of intimate partner violence.

From a victim's physical health perspective, at the centre of any case of intimate partner violence (IPV) is the degree of trauma imparted on that victim by the offender. Yet, the implementations of state-level 'Mandatory Arrest' and 'Preferred Arrest' laws encourage arrests decisions in cases of IPV typically without regard to the level of trauma severity found in each case. And, despite these well-meaning implementations and the gravity of their consequences, the importance of evaluating trauma severity in victims of IPV remains largely overlooked. The goal of this study was to correlate police arrest decisions in cases of IPV to a trauma severity score generated from established clinical protocols in the treatment of trauma. A Trauma Severity Quantification Table (TSQT) was created in order to quantify the major factors of an incident of IPV: anatomical location of attack, method of attack, facilitating weapon/object and resulting trauma. A total of 256 cases of IPV reported to six police departments in Idaho, a state with a discretionary arrest law in domestic violence cases, in the calendar year 2000 were processed using the TSQT. A statistically significant difference was found between arrests (mean 17.96, standard deviation [SD] 5.90) versus no arrest (mean 16.13, SD 5.67) outcomes (P = 0.03). It is suggested that trauma severity is a factor in police arrest decisions in a discretionary state sample, but that more attention needs to be brought to this method of analysis and its implications for future arrest decisions.

A novel stress distribution organ in the arthropod exoskeleton.

The vertebrate endoskeleton possesses a massive internal network of load-distributing trabeculae that in most locations accounts for the vast majority of bone cross sectional area. In contrast, arthropods rely on the external cuticle and its intermittent outpocketings to distribute the daily stresses of physiological loading. One of the constraints of the arthropod exoskeleton is the necessity to house the musculature involved in locomotion, feeding and etc. Because of this lack of an extensive internal load-distributing trabecular network, any load-distributing mechanism in arthropods would necessarily have to incorporate the exoskeleton. Several authors have identified structural apophysi whose functions presumably have mechanical significance, but few have been identified using quantitative analyses. This study investigates a novel stress-reducing structure arising from the articulation sites in the exoskeleton of the blue crab, Callinectes sapidus. During dissection of the merus-carpus joint and leg cuticle of the blue crab, an unique system of internal strut-like members was found radiating, both longitudinally and laterally, from the articular surface of the proximal merus segment, tapering into the diaphyseal region. This strut system, an internal outpocketing of the exoskeleton and semi-circular in cross section, mirrors the trabecular pattern seen radiating from vertebrate joint surfaces. Earlier reports of this structural system described it as a muscle attachment site and made little or no reference to potential load distribution properties. Finite element analysis (FEA) models confirm the efficacy of stress distributing properties of this articular strut system in the blue crab leg. In the models, the struts significantly reduce stress concentrations, reduce localized strains and minimize the risk of failure via buckling. Models lacking this strut system generate 94.7% larger peak von Mises stress at the articulation site, 37% higher peak displacement and 4% greater equivalent strain. The model with the struts is capable of withstanding an applied physiological load of up to 16.6 N prior to buckling, more than twice that of the model without struts (7.8 N). We suggest that this novel arthropod strut system is likely utilized at many joint surfaces at locations of high skeletal stress concentrations, is an adaptation for minimizing skeletal failure via localized buckling, and may be present in other arthropod taxa.

Offender-victim body mass ratio and the decision to arrest in cases of intimate partner violence.

As a result of the growing trend toward criminalisation of cases of domestic violence, there has been a great increase in the number of jurisdictions in the United States that have implemented 'pro-arrest' and 'mandatory arrest' laws. One of the objectives of this legislation is to encourage arrest when there is probable cause to believe that an assault has occurred. Along with the increase in the overall rate of arrest for intimate partner violence there has been a dramatic increase in the arrest of both the parties involved in an incident. In these cases the police do not identify any one party as the primary aggressor. A number of factors may account for this. Analysing these factors can prove beneficial in guiding protocol design and the arresting officer's decision-making process. A yet untested factor that may help explain police arrest practices concerns the relative body mass between the two parties and whether the police use this factor to determine which party is the primary offender. In this study we examine the basic relationship between offender and victim body masses and arrest decisions in 950 cases from police departments in four states: Connecticut, Idaho, Virginia and Tennessee. Our analysis finds that a significant correlation exists between offenders' and victims' body masses, and the resulting arrest decisions. The cause for this relationship remains unspecified, but may involve several factors such as the ability of a larger offender to inflict trauma on a smaller victim, or simply an arresting officer's perception of offender ability to inflict trauma. The cause of this correlation may have significant implications for arrest protocols in those states currently honouring pro-arrest legislation in cases of domestic violence, and those jurisdictions considering them.

Mechanical stimulation alters tissue differentiation and molecular expression during bone healing.

Further understanding of how mechanical cues modulate skeletal tissue differentiation can identify potential means of enhancing repair following injury or disease. Prior studies examined the effects of mechanical loading on osteogenesis, chondrogenesis, and fibrogenesis in an effort to enhance bony union. However, exploring how mechanical stimuli can divert the bone healing process towards formation of other mesenchymal tissues, as an endpoint, may elucidate new avenues for repair and regeneration of tissues such as cartilage and fibrous tissue. This study investigated the use of mechanical stimulation to promote cartilage rather than bone formation within an osteotomy. Our overall goal was to define skeletal tissue distribution and molecular expression patterns induced by the stimulation. Retired breeder Sprague-Dawley rats (n = 85) underwent production of a mid-diaphyseal, transverse femoral osteotomy followed by external fixation. Beginning on postoperative day 10 and continuing for 1, 2, or 4 weeks, a cyclic bending motion (+35 degrees/-25 degrees at 1 Hz) was applied in the sagittal plane for 15 min/day for 5 consecutive days/week. Control animals experienced continuous rigid fixation. Histological and molecular analyses indicated that stimulation substantially altered normal bone healing. Stimulated specimens exhibited an increase in cartilage volume over time, while control specimens demonstrated bony bridging. Stimulation induced upregulation of cartilage-related genes (COL2A1 and COL10A1) and downregulation of bone morphogenetic proteins (BMPs) -4, -6 and -7. However, BMP-3 was upregulated with stimulation. These findings illustrate that mechanical cues can selectively modulate osteogenesis and chondrogenesis in vivo, and suggest a potential basis for treatment regimens for injured or diseased cartilaginous tissues.

Osteogenic effects of traumatic brain injury on experimental fracture-healing.

BACKGROUND: Heterotopic bone formation has been observed in patients with traumatic brain injury; however, an association between such an injury and enhanced fracture-healing remains unclear. To test the hypothesis that traumatic brain injury causes a systemic response that enhances fracture-healing, we established a reproducible model of traumatic brain injury in association with a standard closed fracture and measured the osteogenic response with an in vitro cell assay and assessed bone-healing with biomechanical testing. METHODS: A standard closed femoral fracture was produced in forty-three Sprague-Dawley rats. Twenty-three of the rats were subjected to additional closed head trauma that produced diffuse axonal injury similar to that observed in patients with a traumatic brain injury. Twenty-one days after the procedure, all animals were killed and fracture-healing was assessed by measuring callus size and by mechanical testing. Sera from the animals were used in subsequent in vitro experiments to measure mitogenic effects on established cell lines of committed osteoblasts, fibroblasts, and mesenchymal stem cells. RESULTS: Biomechanical assessment demonstrated that the brain-injury group had increased stiffness (p = 0.02) compared with the fracture-only group. There was no significant difference in torsional strength between the two groups. Cell culture studies showed a significant increase in the proliferative response of mesenchymal stem cells after exposure to sera from the brain-injury group compared with the response after exposure to sera from the fracture-only group (p = 0.0002). This effect was not observed in fibroblasts or committed osteoblasts. CONCLUSIONS: These results support data from previous studies that have suggested an increased osteogenic potential and an enhancement of fracture-healing secondary to traumatic brain injury. Our results further suggest that the mechanism for this enhancement is related to the presence of factors in the serum that have a mitogenic effect on undifferentiated mesenchymal stem cells.

Effects of the local mechanical environment on vertebrate tissue differentiation during repair: does repair recapitulate development?

The local mechanical environment is a crucial factor in determining cell and tissue differentiation during vertebrate skeletal development and repair. Unlike the basic response of bone to mechanical load, as described in Wolff's law, the mechanobiological relationship between the local mechanical environment and tissue differentiation influences everything from tissue type and molecular architecture to the formation of complex joints. This study tests the hypothesis that precisely controlled mechanical loading can regulate gene expression, tissue differentiation and tissue architecture in the adult skeleton and that precise manipulation of the defect's local mechanical environment can initiate a limited recapitulation of joint tissue development. We generated tissue type predictions using finite element models (FEMs) interpreted by published mechanobiological fate maps of tissue differentiation. The experiment included a custom-designed external fixator capable of introducing daily bending, shear or a combination of bending and shear load regimens to induce precisely controlled mechanical conditions within healing femoral defects. Tissue types and ratios were characterized using histomorphometrics and molecular markers. Tissue molecular architecture was quantified using polarized light and Fourier transforms, while immunological staining and in situ hybridization were used to characterize gene expression. The finite element models predicted the differentiation of cartilage within the defects and that substantial fibrous tissues would develop along the extreme excursion peripheries in the bending group. The three experimentally induced loading regimens produced contiguous cartilage bands across all experimental defects, inhibiting bony healing. Histomorphometric analysis of the ratios of cartilage to bone in the experimental groups were not significantly different from those for the knee joint, and Fourier transform analysis determined significantly different collagen fibril angle specializations within superficial, intermediate and deep layers of all experimental cartilages (P<0.0001), approximating those for articular cartilage. All stimulations resulted in the expression of collagen type II, while the bending stimulation also resulted in the expression of the joint-determining gene GDF-5. These findings indicate that the local mechanical environment is an important regulator of gene expression, tissue differentiation and tissue architecture.

Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) specifically inhibit cyclooxygenase (COX) activity and are widely used as anti-arthritics, post-surgical analgesics, and for the relief of acute musculoskeletal pain. Recent studies suggest that non-specific NSAIDs, which inhibit both COX-1 and COX-2 isoforms, delay bone healing. The objectives of this study were 2-fold; first, to measure the relative changes in the normal expression of COX-1 and COX-2 mRNAs over a 42 day period of fracture healing and second, to compare the effects of a commonly used non-specific NSAID, ketorolac, with a COX-2 specific NSAID, Parecoxib (a pro-drug of valdecoxib), on this process. Simple, closed, transverse fractures were generated in femora of male Sprague-Dawley rats weighing approximately 450 g each. Total RNA was prepared from the calluses obtained prior to fracture and at 1, 3, 5, 7, 10, 14, 21, 35 and 42 days post-fracture and levels of COX-1 and COX-2 mRNA were measured using real time PCR. While the relative levels of COX-1 mRNA remained constant over a 21-day period, COX-2 mRNA levels showed peak expression during the first 14 days of healing and returned to basal levels by day 21. Mechanical properties of the calluses were then assessed at 21 and 35 days post-fracture in untreated animals and animals treated with either ketorolac or high or low dose parecoxib. At both 21 and 35 days after fracture, calluses in the group treated with the ketorolac showed a significant reduction in mechanical strength and stiffness when compared with controls (p<0.05). At the 21-day time point, calluses of the parecoxib treated animals showed a lower mean mechanical strength than controls, but the inhibition was not statistically significant. Based on physical analysis of the bones, 3 of 12 (25%) of the ketorolac-treated and 1 of 12 (8%) of the high dose parecoxib-treated animals showed failure to unite their fractures by 21 days, while all fractures in both groups showed union by 35 days. Histological analysis at 21 days showed that the calluses in the ketorolac-treated group contained substantial amounts of residual cartilage while neither the control nor the parecoxib-treated animals showed comparable amounts of cartilage at this stage. These results demonstrate that ketorolac and parecoxib delay fracture healing in this model, but in this study daily administration of ketorolac, a non-selective COX inhibitor had a greater affect on this process. They further demonstrate that a COX-2 selective NSAID, such as parecoxib (valdecoxib), has only a small effect on delaying fracture healing even at doses that are known to fully inhibit prostaglandin production.

Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation.

Fracture healing is a specialized post-natal repair process that recapitulates aspects of embryological skeletal development. While many of the molecular mechanisms that control cellular differentiation and growth during embryogenesis recur during fracture healing, these processes take place in a post-natal environment that is unique and distinct from those which exist during embryogenesis. This Prospect Article will highlight a number of central biological processes that are believed to be crucial in the embryonic differentiation and growth of skeletal tissues and review the functional role of these processes during fracture healing. Specific aspects of fracture healing that will be considered in relation to embryological development are: (1) the anatomic structure of the fracture callus as it evolves during healing; (2) the origins of stem cells and morphogenetic signals that facilitate the repair process; (3) the role of the biomechanical environment in controlling cellular differentiation during repair; (4) the role of three key groups of soluble factors, pro-inflammatory cytokines, the TGF-beta superfamily, and angiogenic factors, during repair; and (5) the relationship of the genetic components that control bone mass and remodeling to the mechanisms that control skeletal tissue repair in response to fracture.

The effect of recombinant human osteogenic protein-1 (bone morphogenetic protein-7) impregnation on allografts in a canine intercalary bone defect.

The utility of cortical allografts in repairing large bone defects is limited by their slow and incomplete incorporation into host bone. In order to determine the effects of recombinant human osteogenic protein-1 (rhOP-1) impregnation on allograft incorporation, we used a canine intercalary bone defect model. Bilateral resection of a 4 cm segment of the femoral diaphysis and reconstruction with structural bone allografts were performed. In one limb, the allograft was soaked in solution with rhOP-1 for 1 h before implantation. In the other limb, the allograft was soaked in the same solution without rhOP-1. Dynamic load-bearing, radiographic analysis, biomechanical testing, and histomorphometric analysis were conducted. Radiographic analysis showed significantly larger periosteal callus area in the rhOP-1 treated group at week 2. The rhOP-1 significantly increased allograft bone porosity and significantly increased the number of active osteons in the allografts. There were no significant differences between the rhOP-1 treated and non-treated allografts in load bearing and biomechanical analyses. These findings indicate that rhOP- I increases intercalary allograft remodeling without deleterious effects in mechanical and functional strength.

Induction of a neoarthrosis by precisely controlled motion in an experimental mid-femoral defect.

Bone regeneration during fracture healing has been demonstrated repeatedly, yet the regeneration of articular cartilage and joints has not yet been achieved. It has been recognized however that the mechanical environment during fracture healing can be correlated to the contributions of either the endochondral or intramembranous processes of bone formation, and to resultant tissue architecture. Using this information, the goal of this study was to test the hypothesis that induced motion can directly regulate osteogenic and chondrogenic tissue formation in a rat mid-femoral bone defect and thereby influence the anatomical result. Sixteen male Sprague Dawley rats (400 +/- 20 g) underwent production of a mid-diaphyseal, non-critical sized 3.0 mm segmental femoral defect with rigid external fixation using a custom designed four pin fixator. One group of eight animals represented the controls and underwent surgery and constant rigid fixation. In the treatment group the custom external fixator was used to introduce daily interfragmentary bending strain in the eight treatment animals (12 degree angular excursion), with a hypothetical symmetrical bending load centered within the gap. The eight animals in the treatment group received motion at 1.0 Hz, for 10 min a day, with a 3 days on, one day off loading protocol for the first two weeks, and 2 days on, one day off for the remaining three weeks. Data collection included histological and immunohistological identification of tissue types, and mean collagen fiber angles and angular conformity between individual fibers in superficial, intermediate, and deep zones within the cartilage. These parameters were compared between the treatment group, rat knee articular cartilage, and the control group as a structural outcome assessment. After 35 days the control animals demonstrated varying degrees of osseous union of the defect with some animals showing partial union. In every individual within the mechanical treatment group the defect completely failed to unite. Bony arcades developed in the experimental group, capping the termini of the bone segments on both sides of the defect in four out of six animals completing the study. These new structures were typically covered with cartilage, as identified by specific histological staining for Type II collagen and proteoglycans. The distribution of collagen within analogous superficial, intermediate, and deep zones of the newly formed cartilage tissue demonstrated preferred fiber angles consistent with those seen in articular cartilage. Although not resulting in complete joint development, these neoarthroses show that the induced motion selectively controlled the formation of cartilage and bone during fracture repair, and that it can be specifically directed. They further demonstrate that the spatial organization of molecular components within the newly formed tissue, at both microanatomical and gross levels, are influenced by their local mechanical environment, confirming previous theoretical models.