ABSTRACT
There is a significant need for models that can capture the mechanical behavior of complex porous lattice architectures produced by 3D printing. The free boundary effect is an experimentally observed behavior of lattice architectures including the gyroid triply periodic minimal surface where the number of unit cell repeats has been shown to influence the mechanical performance of the lattice. The purpose of this study is to use finite element modeling to investigate how architecture porosity, unit cell size, and sample size dictate mechanical behavior. Samples with varying porosity and increasing number of unit cells (relative to sample size) were modeled under an axial compressive load to determine the effective modulus. The finite element model captured the free boundary effect and captured experimental trends in the structure's modulus. The findings of this study show that samples with higher porosity are more susceptible to the impact of the free boundary effect and in some samples, the modulus can be 20% smaller in samples with smaller numbers of unit cell repeats within a given sample boundary. The outcomes from this study provide a deeper understanding of the gyroid structure and the implications of design choices including porosity, unit cell size, and overall sample size.
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PURPOSE OF REVIEW: Obesity is highly prevalent and is associated with bone fragility and fracture. The changing nutrient availability to bone in obesity is an important facet of bone health. The goal of this article is to summarize current knowledge on the effects of carbohydrate and dietary fat availability on bone, particularly in the context of other tissues. RECENT FINDINGS: The skeleton is a primary site for fatty acid and glucose uptake. The trafficking of carbohydrates and fats into tissues changes with weight loss and periods of weight gain. Exercise acutely influences nutrient uptake into bone and may affect nutrient partitioning to bone. Bone cells secrete hormones that signal to the brain and other tissues information about its energetic state, which may alter whole-body nutrient trafficking. There is a critical need for studies to address the changes that metabolic perturbations have on nutrient availability in bone.
Subject(s)
Bone Density , Obesity , Humans , Obesity/metabolism , Dietary Fats/metabolism , Energy Metabolism , Nutrients , Energy IntakeABSTRACT
AIMS: To determine differences in hip geometry in adults with type 1 diabetes (T1D) compared with healthy adults without diabetes. METHODS: In this cross-sectional study, 43 adults with T1D (mean age 56 years, 84 % female, 92 % White, mean duration of diabetes of 39 years, A1c of 7.8 %) and 40 adults without diabetes (mean age 60 years, 80 % female, 77 % white) who had hip dual-energy x-ray absorptiometry (DXA) scans from previous studies were included. Areal bone mineral density (aBMD) and measures of hip structural properties at the narrow neck, intertrochanteric and femoral shaft regions of the left proximal femur were analyzed between adults with T1D and controls using linear models controlled for age, sex, and body mass index. RESULTS: There were no significant differences in DXA-based aBMD at the hip (0.769 ± 0.132 vs. 0.900 ± 0.139 g/cm2, p = 0.07) or femoral neck (0.722 ± 0.116 vs. 0.849 ± 0.114 g/cm2, p = 0.09) regions between adults with T1D and controls. When controlling for age, sex, and BMI, DXA-based aBMD at the hip (0.880 ± 0.022 vs. 0.943 ± 0.020 g/cm2, p = 0.02) and femoral neck (0.750 ± 0.021 vs. 0.812 ± 0.020 g/cm2, p = 0.02) regions were significantly lower in adults with T1D than controls. Cortical thickness was significantly lower in all three hip regions in adults with T1D than in controls (narrow-neck: 0.169 ± 0.005 vs. 0.186 ± 0.005 cm, p = 0.011; intertrochanteric: 0.388 ± 0.013 vs. 0.425 ± 0.012 cm, p = 0.017; femoral shaft: 0.529 ± 0.017 vs. 0.586 ± 0.016 cm, p = 0.006). Moreover, adults with T1D had a smaller cross-sectional area at the narrow-neck (3.06 ± 0.09 vs. 3.32 ± 0.08 cm2, p = 0.015), a higher femoral shaft endocortical diameter (2.23 ± 0.07 vs. 2.02 ± 0.06 cm, p = 0.011), and higher buckling ratios (an indicator of cortical instability) at the intertrochanteric (9.22 ± 0.34 vs. 8.23 ± 0.32, p = 0.016) and femoral shaft (3.32 ± 0.15 vs. 2.89 ± 0.14, p = 0.016) regions. CONCLUSIONS: Adults with T1D have several significant differences in proximal femur morphology compared with controls. These morphological differences may adversely affect the mechanical integrity of the proximal femur, thereby contributing to an increased risk of fracture in the event of a fall.
Subject(s)
Diabetes Mellitus, Type 1 , Femur Neck , Adult , Female , Humans , Middle Aged , Male , Femur Neck/diagnostic imaging , Diabetes Mellitus, Type 1/complications , Cross-Sectional Studies , Absorptiometry, Photon , Bone DensityABSTRACT
OBJECTIVE: Since the COVID-19 pandemic began in early 2020, SARS-CoV2 has claimed more than six million lives world-wide, with over 510 million cases to date. To reduce healthcare burden, we must investigate how to prevent non-acute disease from progressing to severe infection requiring hospitalization. METHODS: To achieve this goal, we investigated metabolic signatures of both non-acute (out-patient) and severe (requiring hospitalization) COVID-19 samples by profiling the associated plasma metabolomes of 84 COVID-19 positive University of Virginia hospital patients. We utilized supervised and unsupervised machine learning and metabolic modeling approaches to identify key metabolic drivers that are predictive of COVID-19 disease severity. Using metabolic pathway enrichment analysis, we explored potential metabolic mechanisms that link these markers to disease progression. RESULTS: Enriched metabolites associated with tryptophan in non-acute COVID-19 samples suggest mitigated innate immune system inflammatory response and immunopathology related lung damage prevention. Increased prevalence of histidine- and ketone-related metabolism in severe COVID-19 samples offers potential mechanistic insight to musculoskeletal degeneration-induced muscular weakness and host metabolism that has been hijacked by SARS-CoV2 infection to increase viral replication and invasion. CONCLUSIONS: Our findings highlight the metabolic transition from an innate immune response coupled with inflammatory pathway inhibition in non-acute infection to rampant inflammation and associated metabolic systemic dysfunction in severe COVID-19.
Subject(s)
COVID-19 , Humans , Inflammation , Metabolomics , Pandemics , RNA, Viral , SARS-CoV-2 , Severity of Illness IndexABSTRACT
We describe the development and validation of a Sudden Unexpected Death in Infancy (SUDI) risk assessment clinical tool. An initial SUDI risk assessment algorithm was developed from an individual participant data meta-analysis of five international SIDS/SUDI case-control studies. The algorithm was translated into a clinical web tool called the Safe Sleep Calculator, which was tested at the routine infant 6-week check-up in primary care clinics in New Zealand. Evidence was gathered through mixed-methods research to inform the revision of the algorithm and the clinical tool. The revised algorithm performance was validated on a new contemporary New Zealand SUDI case-control study dataset and the pilot population data set. The area under the Receiver Operator Characteristic (ROC) curve is 0.89, with a sensitivity of 83.0% and a specificity of 80.9% in the NZ infant population when 0.3 per 1000 live births or more risk is used to define 'at higher risk'. The Safe Sleep Calculator SUDI risk assessment tool provides individualized evidence-based specific SUDI prevention advice for every infant and enables the concentration of additional SUDI prevention efforts and resource for infants at higher risk.
Subject(s)
Sudden Infant Death , Case-Control Studies , Humans , Infant , Risk Assessment , Risk Factors , Sleep , Sudden Infant Death/epidemiology , Sudden Infant Death/etiology , Sudden Infant Death/prevention & controlABSTRACT
The NFL recently released validated helmet-impact models to study the performance of currently used helmets. This study used the model of a Riddell Speed Classic helmet to determine the influence of the properties of protective foam padding on acceleration and deformation at two common impact locations to cause concussions. The performance of the helmet was measured before and after manipulating the material properties of the protective foam liner material using FEA software. The densification strain was adjusted by using the scale factor tool in LS-DYNA to create four material categories - soft, standard, stiff, and rigid. The helmet was tested under side and rear impacts using the four material properties at 2.0, 5.5, 7.4, 9.3 and 12.3 m/s impact speeds using the NOCSAE linear impactor model. This study suggests that the standard foam material compresses to a range that could be considered to have "bottomed out" at impact speeds at 5.5 m/s for side impacts. Despite testing a wide range of material properties, the measured accelerations did not vary dramatically across material properties. Rather, impact speed played the dominant role on measured acceleration. This is the first study to demonstrate how open-source impact models can be used to run a design of experiments and investigate the role between different materials used inside a helmet and football helmet performance.
Subject(s)
Computer Simulation , Football , Head Protective Devices , Acceleration , Biomechanical Phenomena , Head , Humans , Models, AnatomicABSTRACT
Oculomotor decision making can be investigated by a simple step task, where a person decides whether a target has jumped to the left or the right. More complex tasks include the countermanding task (look at the jumped target, except when a subsequent signal instructs you not to) and the Wheeless task (where the jumped target sometimes then quickly jumps to a new location). Different instantiations of the LATER (Linear Approach to Threshold with Ergodic Rate) model have been shown to explain the saccadic latency data arising from these tasks, despite it being almost inconceivable that completely separate decision-making mechanisms exist for each. However, these models have an identical construction with regards to predicting prosaccadic responses (all step task trials, and control trials in countermanding and Wheeless tasks, where no countermanding signal is given or when the target does not make a second jump). We measured saccadic latencies for 23 human observers each performing the three tasks, and modelled prosaccade latencies with LATER to see if model parameters were usefully preserved across tasks. We found no significant difference in reaction times and model parameters between the step and Wheeless tasks (mean 175 and 177â¯ms, respectively; standard deviation, SD 22 and 24â¯ms). In contrast, we identified prolonged latencies in the countermanding tasks (236â¯ms; SD 37â¯ms) explained by a slower rise and an elevated threshold of the decision making signal, suggesting elevated participant caution. Our findings support the idea that common machinery exists for oculomotor decision-making, which can be flexibly deployed depending upon task demands.
Subject(s)
Psychomotor Performance , Saccades , Humans , Photic Stimulation , Reaction TimeABSTRACT
The purpose of this study was to determine whether obesity and/or exercise training alters weight regain and musculoskeletal health after ovariectomy (OVX). Female rats were fed high-fat diet (HFD) to reveal obesity-prone (OP) and obesity-resistant (OR) phenotypes. The OP and OR exercising (EX) and sedentary (SED) rats were calorically restricted to lose 15% of body weight using medium-fat diet. Rats were then maintained in energy balance for 8 wk before OVX. After OVX and a brief calorically limited phase, rats were allowed to eat ad libitum until body weight plateaued. Starting at weight loss, EX ran 1 h·d, 6 d·wk, 15 m·min. Energy intake, spontaneous physical activity (SPA), and total energy expenditure were evaluated at the end of weight maintenance pre-OVX, and at three time points post-OVX: before weight regain, during early regain, and after regain. Data are presented as mean ± SE. Exercise attenuated weight regain after OVX in OP only (OP-EX, 123 ± 10 g; OP-SED, 165 ± 12 g; OR-EX, 121 ± 6 g; OR-SED, 116 ± 6 g), which was primarily an attenuation of fat gain. The early post-OVX increase in energy intake explained much of the weight regain, and was similar across groups. Exercising improved bone strength, as did maintaining SPA. Group differences in muscle mitochondrial respiration were not significant. The large decrease in SPA due to OVX was persistent, but early weight regain was dependent on decreased SPA. In conclusion, leanness and exercise do not necessarily protect from OVX-induced weight gain. Exercise prevented weight gain in obese rats, but loss of SPA was the greatest contributor to post-OVX weight gain. Thus, understanding the mechanisms resulting in reduction in SPA after ovarian hormone loss is critical in the prevention of menopause-associated metabolic dysfunction.
Subject(s)
Bone Density/physiology , Menopause/physiology , Mitochondria, Muscle/physiology , Obesity/physiopathology , Oxygen Consumption/physiology , Physical Conditioning, Animal/physiology , Weight Gain/physiology , Animals , Body Composition/physiology , Energy Metabolism , Female , Models, Animal , Muscle, Skeletal/physiology , Ovariectomy , Rats, WistarABSTRACT
Chronic kidney disease (CKD) is a common disease of aging and increases fracture risk over advanced age alone. Aging and CKD differently impair bone turnover and mineralization. We thus hypothesize that the loss of bone quality would be greatest with the combination of advanced age and CKD. We evaluated bone from young adult (6 mo.), middle-age (18 mo.), and old (24 mo.) male C57Bl/6 mice three months following either 5/6th nephrectomy, to induce CKD, or Sham procedures. CKD exacerbated losses of cortical and trabecular microarchitecture associated with aging. Aging and CKD each resulted in thinner, more porous cortices and fewer and thinner trabeculae. Bone material quality was also reduced with CKD, and these changes to bone material were distinct from those due to age. Aging reduced whole-bone flexural strength and modulus, micrometer-scale nanoindentation modulus, and nanometer-scale tissue and collagen strain (small-angle x-ray scattering [SAXS]. By contrast, CKD reduced work to fracture and variation in bone tissue modulus and composition (Raman spectroscopy), and increased percent collagen strain. The increased collagen strain burden was associated with loss of toughness in CKD. In addition, osteocyte lacunae became smaller, sparser, and more disordered with age for Sham mice, yet these age-related changes were not clearly observed in CKD. However, for CKD, larger lacunae positively correlated with increased serum phosphate levels, suggesting that osteocytes play a role in systemic mineral homeostasis. This work demonstrates that CKD reduces bone quality, including microarchitecture and bone material properties, and that loss of bone quality with age is compounded by CKD. These findings may help reconcile why bone mass does not consistently predict fracture in the CKD population, as well as why older individuals with CKD are at high risk of fragility.
Subject(s)
Aging/pathology , Bone and Bones/pathology , Renal Insufficiency, Chronic/pathology , Animals , Biomechanical Phenomena , Cancellous Bone/diagnostic imaging , Cancellous Bone/pathology , Collagen/metabolism , Cortical Bone/diagnostic imaging , Cortical Bone/pathology , Finite Element Analysis , Imaging, Three-Dimensional , Male , Mice, Inbred C57BL , Osteocytes/pathology , Regression Analysis , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/diagnostic imaging , Renal Insufficiency, Chronic/urine , Reproducibility of Results , Scattering, Small Angle , Tibia/pathology , X-Ray Diffraction , X-Ray MicrotomographyABSTRACT
Women with type 1 diabetes (T1D) are at increased risk for fracture. We studied the association of T1D and young age at T1D onset (T1D onset before 20â¯years) on bone structural quality. 24 postmenopausal women with T1D (mean age 60.9â¯years, mean T1D duration 41.7â¯years) and 22 age, sex- and body mass index (BMI)-matched controls underwent dual X-ray absorptiometry (DXA) measured areal bone mineral density (aBMD) at the lumbar spine, hip and distal radius. Bone mass, geometry and estimated bone strength were assessed at distal and shaft of non-dominant radius and tibia using peripheral quantitative computed tomography (pQCT). Postmenopausal women with T1D had lower trabecular volumetric bone mineral density (vBMD) (LSM⯱â¯SEM; 166.1⯱â¯8.2 vs 195.9⯱â¯8.3â¯mg/cm3, pâ¯=â¯0.02) and compressive bone strength (24.6⯱â¯1.8 vs 30.1⯱â¯1.9â¯mg2/mm4, pâ¯=â¯0.04) at the distal radius compared to controls adjusting for age, BMI and radius length. At the distal radius, patients with young onset T1D had lower total vBMD (258.7⯱â¯19.7 vs 350.8⯱â¯26.1â¯mg/cm3, pâ¯=â¯0.02) and trabecular vBMD (141.4⯱â¯11.6 vs 213.6⯱â¯15.4â¯mg/cm3, pâ¯=â¯0.003) compared to adult onset T1D patients adjusting for age, BMI and the radius length. At the tibial shaft, young onset T1D patients had larger endosteal circumference (39.1⯱â¯1.2 vs 32.1⯱â¯1.6â¯mm, pâ¯=â¯0.005) with similar periosteal circumference (67.1⯱â¯0.9 vs 65.1⯱â¯1.2â¯mm, pâ¯=â¯0.2) resulting in reduced cortical thickness (4.4⯱â¯0.1 vs 5.2⯱â¯0.1â¯mm, pâ¯=â¯0.004) compared to adult onset T1D patients adjusting for age, BMI and the tibia length. There was no difference in the lumbar spine, femoral neck, total hip and distal radius DXA-measured aBMD between subjects with T1D and controls. T1D is associated with lower trabecular vBMD at the distal radius. T1D onset before age 20 is associated with cortical bone size deficits at the tibial shaft.
Subject(s)
Diabetes Mellitus, Type 1/physiopathology , Osteoporosis, Postmenopausal/metabolism , Body Mass Index , Bone Density/physiology , Bone Diseases, Metabolic/physiopathology , Cross-Sectional Studies , Female , Femur Neck/physiology , Humans , Radius/physiology , Tibia/physiologyABSTRACT
For those patients who suffer from low back pain generated by the sacroiliac (SI) joint, fusion of the SI joint has proven to be an effective means of stabilizing it and reducing pain. Though it has shown promise, SI joint fusion raises clinical questions regarding its effect on neighboring joints such as the hip. As such, the purpose of this study was to determine the effects of SI joint fixation on the hip. A finite element spine-sacroiliac-hip (SSIH) model was developed and its functionality was verified against SI joint range of motion (ROM) and hip contact stress, respectively. The intact model was fixed in double leg stance at the distal femora, and loading was applied at the lumbar spine to simulate stance, flexion, extension, right and left lateral bending, and right and left axial rotation. Functionality was confirmed by measuring and comparing SI joint ROM and contact stress and area at the hip with data from the literature. Following verification of the intact SSIH model, both unilateral and bilateral SI joint fixation were modeled; hip contact stress and area were compared to the intact state. Average hip contact stress was ~2 MPa, with most motions resulting in changes less than 5% relative to intact; contact area changed less than 10% for any motion. Clinical significance: these results demonstrated that SI joint fixation with triangular titanium implants imparted little change in stress at the hip, which suggests that the risk of developing adjacent segment disease is likely low. Future clinical studies may be executed to confirm the results of this computational study.
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Current implant materials and designs used in spinal fusion show high rates of subsidence. There is currently a need for a method to predict the mechanical properties of the endplate using clinically available tools. The purpose of this study was to develop a predictive model of the mechanical properties of the vertebral endplate at a scale relevant to the evaluation of current medical implant designs and materials. Twenty vertebrae (10 L1 and 10 L2) from 10 cadavers were studied using dual-energy X-ray absorptiometry to define bone status (normal, osteopenic, or osteoporotic) and computed tomography (CT) to study endplate thickness (µm), density (mg/mm3), and mineral density of underlying trabecular bone (mg/mm3) at discrete sites. Apparent Oliver-Pharr modulus, stiffness, maximum tolerable pressure (MTP), and Brinell hardness were measured at each site using a 3 mm spherical indenter. Predictive models were built for each measured property using various measures obtained from CT and demographic data. Stiffness showed a strong correlation between the predictive model and experimental values (r = 0.85), a polynomial model for Brinell hardness had a stronger predictive ability compared to the linear model (r = 0.82), and the modulus model showed weak predictive ability (r = 0.44), likely due the low indentation depth and the inability to image the endplate at that depth (≈0.15 mm). Osteoporosis and osteopenia were found to be the largest confounders of the measured properties, decreasing them by approximately 50%. It was confirmed that vertebral endplate mechanical properties could be predicted using CT and demographic indices.
Subject(s)
Lumbar Vertebrae/diagnostic imaging , Mechanical Phenomena , Adult , Aged , Biomechanical Phenomena , Female , Hardness , Humans , Lumbar Vertebrae/physiology , Male , Materials Testing , Middle Aged , Tomography, X-Ray ComputedABSTRACT
This set of experiments characterizes a model of transient cerebral ischemic stroke in a transgenic (Tg) mouse line in which the glial fibrillary acidic protein (GFAP) promoter is utilized to drive expression of a human RNA-binding protein, HuR. Additionally, the effect of cerebral ischemia on the expression of endogenous Hu proteins is presented.
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Bone daggers were once widespread in New Guinea. Their purpose was both symbolic and utilitarian; they functioned as objects of artistic expression with the primary function of stabbing and killing people at close quarters. Most daggers were shaped from the tibiotarsus of cassowaries, but daggers shaped from the femora of respected men carried greater social prestige. The greater cross-sectional curvature of human bone daggers indicates superior strength, but the material properties of cassowary bone are unknown. It is, therefore, uncertain whether the macrostructure of human bone daggers exists to compensate for inferior material properties of human femora or to preserve the symbolic value of a prestigious object. To explore this question, we used computed tomography to examine the structural mechanics of 11 bone daggers, 10 of which are museum-accessioned objects of art. We found that human and cassowary bones have similar material properties and that the geometry of human bone daggers results in higher moments of inertia and a greater resistance to bending. Data from finite-element models corroborated the superior mechanical performance of human bone daggers, revealing greater resistance to larger loads with fewer failed elements. Taken together, our findings suggest that human bone daggers were engineered to preserve symbolic capital, an outcome that agrees well with the predictions of signalling theory.
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PURPOSE OF REVIEW: This article reviews recent publications on the effect of type 1 diabetes (T1D) on fracture risk, bone mineral density (BMD), bone structure, and bone tissue quality. Possible fracture prevention strategies for patients with T1D have also been reviewed. RECENT FINDINGS: T1D is associated with substantially elevated fracture risk and modestly low BMD at the femoral neck. However, BMD alone does not explain higher observed fracture risk in T1D. T1D also affects bone macro- and microstructure, characterized by thinner cortices and trabecular bone changes such as thinner and more widely spaced trabeculae. Structural bone deficit is pronounced in the presence of microvascular complications. Tissue-level changes, such as accumulation of advanced glycation endproducts, detrimental alterations of the mineral phase because of low bone turnover, and occlusion of vascular channels in bone by mineralized tissue, are implicated in pathophysiology of bone fragility in T1D. There are no guidelines on screening and prevention of osteoporotic fractures in T1D. SUMMARY: More studies are needed to understand the influence of T1D on structural bone quality and tissue material properties. There is a need for a prospective study to evaluate better screening strategies for diagnosis and treatment of osteoporosis in T1D.
Subject(s)
Bone Diseases/epidemiology , Diabetes Mellitus, Type 1/complications , Bone Density , Bone Diseases/etiology , Bone Remodeling , Bone and Bones/blood supply , Bone and Bones/pathology , Cancellous Bone , Diabetes Complications , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 1/physiopathology , Female , Femur Neck , Fractures, Bone/epidemiology , Fractures, Bone/prevention & control , Humans , Osteoporosis/diagnosis , Osteoporosis/epidemiology , Osteoporosis/therapy , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , Risk FactorsABSTRACT
BACKGROUND: Handwashing sink drains are increasingly implicated as a potential reservoir of antibiotic-resistant bacteria in hospital outbreaks; however, usage patterns that may promote this source remain unknown. AIM: To understand behaviours in the intensive care unit (ICU) that may facilitate establishment and nosocomial transmission of multidrug-resistant Gram negatives from a sink-trap reservoir to a patient. METHODS: Motion-sensitive cameras captured anonymized activity paired with periodic in-person observations during a quality investigation from four ICU sinks (two patient rooms and two patient bathrooms) in a university hospital. FINDINGS: We analysed 4810 sink videos from 60 days in patient rooms (3625) and adjoining bathrooms (1185). There was a false-positive rate of 38% (1837 out of 4810) in which the camera triggered but no sink interaction occurred. Of the 2973 videos with analysed behaviours there were 5614 observed behaviours which were assessed as: 37.4% medical care, 29.2% additional behaviours, 17.0% hand hygiene, 7.2% patient nutrition, 5.0% environmental care, 4.2% non-medical care. Handwashing was only 4% (224 out of 5614) of total behaviours. Sub-analysis of 2748 of the later videos further categorized 56 activities where a variety of nutrients, which could promote microbial growth, were disposed of in the sink. CONCLUSION: Several non-hand hygiene activities took place regularly in ICU handwashing sinks; these may provide a mechanism for nosocomial transmission and promotion of bacterial growth in the drain. Redesigning hospital workflow and sink usage may be necessary as it becomes apparent that sink drains may be a reservoir for transmission of multidrug-resistant bacteria.
Subject(s)
Environmental Microbiology , Hand Disinfection , Intensive Care Units , Cross Infection/epidemiology , Cross Infection/prevention & control , Disease Transmission, Infectious/prevention & control , Hospitals , Humans , Pilot ProjectsABSTRACT
Poly(para-phenylene) (PPP) is a novel aromatic polymer with higher strength and stiffness than polyetheretherketone (PEEK), the gold standard material for polymeric load-bearing orthopaedic implants. The amorphous structure of PPP makes it relatively straightforward to manufacture different architectures, while maintaining mechanical properties. PPP is promising as a potential orthopaedic material; however, the biocompatibility and osseointegration have not been well investigated. The objective of this study was to evaluate biological and mechanical behavior of PPP, with or without porosity, in comparison to PEEK. We examined four specific constructs: 1) solid PPP, 2) solid PEEK, 3) porous PPP and 4) porous PEEK. Pre-osteoblasts (MC3T3) exhibited similar cell proliferation among the materials. Osteogenic potential was significantly increased in the porous PPP scaffold as assessed by ALP activity and calcium mineralization. In vivo osseointegration was assessed by implanting the cylindrical materials into a defect in the metaphysis region of rat tibiae. Significantly more mineral ingrowth was observed in both porous scaffolds compared to the solid scaffolds, and porous PPP had a further increase compared to porous PEEK. Additionally, porous PPP implants showed bone formation throughout the porous structure when observed via histology. A computational simulation of mechanical push-out strength showed approximately 50% higher interfacial strength in the porous PPP implants compared to the porous PEEK implants and similar stress dissipation. These data demonstrate the potential utility of PPP for orthopaedic applications and show improved osseointegration when compared to the currently available polymeric material. STATEMENT OF SIGNIFICANCE: PEEK has been widely used in orthopaedic surgery; however, the ability to utilize PEEK for advanced fabrication methods, such as 3D printing and tailored porosity, remain challenging. We present a promising new orthopaedic biomaterial, Poly(para-phenylene) (PPP), which is a novel class of aromatic polymers with higher strength and stiffness than polyetheretherketone (PEEK). PPP has exceptional mechanical strength and stiffness due to its repeating aromatic rings that provide strong anti-rotational biaryl bonds. Furthermore, PPP has an amorphous structure making it relatively easier to manufacture (via molding or solvent-casting techniques) into different geometries with and without porosity. This ability to manufacture different architectures and use different processes while maintaining mechanical properties makes PPP a very promising potential orthopaedic biomaterial which may allow for closer matching of mechanical properties between the host bone tissue while also allowing for enhanced osseointegration. In this manuscript, we look at the potential of porous and solid PPP in comparison to PEEK. We measured the mechanical properties of PPP and PEEK scaffolds, tested these scaffolds in vitro for osteocompatibility with MC3T3 cells, and then tested the osseointegration and subsequent functional integration in vivo in a metaphyseal drill hole model in rat tibia. We found that PPP permits cell adhesion, growth, and mineralization in vitro. In vivo it was found that porous PPP significantly enhanced mineralization into the construct and increased the mechanical strength required to push out the scaffold in comparison to PEEK. This is the first study to investigate the performance of PPP as an orthopaedic biomaterial in vivo. PPP is an attractive material for orthopaedic implants due to the ease of manufacturing and superior mechanical strength.
Subject(s)
Bone-Anchored Prosthesis , Calcification, Physiologic , Implants, Experimental , Materials Testing , Osteogenesis , Polymers/chemistry , Animals , Benzophenones , Cell Line , Ketones , Male , Mice , Polyethylene Glycols , Porosity , Rats , Rats, Sprague-DawleyABSTRACT
Osseointegration of load-bearing orthopaedic implants, including interbody fusion devices, is critical to long-term biomechanical functionality. Mechanical loads are a key regulator of bone tissue remodeling and maintenance, and stress-shielding due to metal orthopaedic implants being much stiffer than bone has been implicated in clinical observations of long-term bone loss in tissue adjacent to implants. Porous features that accommodate bone ingrowth have improved implant fixation in the short term, but long-term retrieval studies have sometimes demonstrated limited, superficial ingrowth into the pore layer of metal implants and aseptic loosening remains a problem for a subset of patients. Polyether-ether-ketone (PEEK) is a widely used orthopaedic material with an elastic modulus more similar to bone than metals, and a manufacturing process to form porous PEEK was recently developed to allow bone ingrowth while preserving strength for load-bearing applications. To investigate the biomechanical implications of porous PEEK compared to porous metals, we analyzed finite element (FE) models of the pore structure-bone interface using two clinically available implants with high (> 60%) porosity, one being constructed from PEEK and the other from electron beam 3D-printed titanium (Ti). The objective of this study was to investigate how porous PEEK and porous Ti mechanical properties affect load sharing with bone within the porous architectures over time. Porous PEEK substantially increased the load share transferred to ingrown bone compared to porous Ti under compression (i.e. at 4 weeks: PEEK = 66%; Ti = 13%), tension (PEEK = 71%; Ti = 12%), and shear (PEEK = 68%; Ti = 9%) at all time points of simulated bone ingrowth. Applying PEEK mechanical properties to the Ti implant geometry and vice versa demonstrated that the observed increases in load sharing with PEEK were primarily due to differences in intrinsic elastic modulus and not pore architecture (i.e. 4 weeks, compression: PEEK material/Ti geometry = 53%; Ti material/PEEK geometry = 12%). Additionally, local tissue energy effective strains on bone tissue adjacent to the implant under spinal load magnitudes were over two-fold higher with porous PEEK than porous Ti (i.e. 4 weeks, compression: PEEK = 784 ± 351 microstrain; Ti = 180 ± 300 microstrain; and 12 weeks, compression: PEEK = 298 ± 88 microstrain; Ti = 121 ± 49 microstrain). The higher local strains on bone tissue in the PEEK pore structure were below previously established thresholds for bone damage but in the range necessary for physiological bone maintenance and adaptation. Placing these strain magnitudes in the context of literature on bone adaptation to mechanical loads, this study suggests that porous PEEK structures may provide a more favorable mechanical environment for bone formation and maintenance under spinal load magnitudes than currently available porous 3D-printed Ti, regardless of the level of bone ingrowth.