Microarchitectural Features Research Articles

A scanning electron microscopy study of projectile entry fractures in cortical bone; genesis and microarchitectural features

The present paper presents a scanning electron microscope (SEM) analysis of the genesis and microarchitecture of experimentally induced cortical entry fractures in porcine scapulae impacted at velocities ranging from 54 to 897 m/s. SEM observation was conducted on polyurethane replicas cast from negative silicone moulds. Analysis of the sequence of fracture processes operative during projectile impact revealed the presence of ring cracks at the site of impact, confirming that penetration in sandwich bones is achieved by cone crack propagation. Despite impulsive loading, two forms of plastic deformation were identified in the cortical bone surrounding the entry fracture up to a maximum velocity of 871 m/s. Microscopic radial and concentric cracks were associated with projectile impact, and the role of pores and pits as stress concentrators was captured. Possible underlying mechanisms for the observed plastic deformation are described, and the diagnostic utility of SEM analysis is presented.

High-resolution mapping and digital atlas of subcortical regions in the macaque monkey based on matched MAP-MRI and histology

Subcortical nuclei and other deep brain structures are known to play an important role in the regulation of the central and peripheral nervous systems. It can be difficult to identify and delineate many of these nuclei and their finer subdivisions in conventional MRI due to their small size, buried location, and often subtle contrast compared to neighboring tissue. To address this problem, we applied a multi-modal approach in ex vivo non-human primate (NHP) brain that includes high-resolution mean apparent propagator (MAP)-MRI and five different histological stains imaged with high-resolution microscopy in the brain of the same subject. By registering these high-dimensional MRI data to high-resolution histology data, we can map the location, boundaries, subdivisions, and micro-architectural features of subcortical gray matter regions in the macaque monkey brain. At high spatial resolution, diffusion MRI in general, and MAP-MRI in particular, can distinguish a large number of deep brain structures, including the larger and smaller white matter fiber tracts as well as architectonic features within various nuclei. Correlation with histology from the same brain enables a thorough validation of the structures identified with MAP-MRI. Moreover, anatomical details that are evident in images of MAP-MRI parameters are not visible in conventional T1-weighted images. We also derived subcortical template “SC21” from segmented MRI slices in three-dimensions and registered this volume to a previously published anatomical template with cortical parcellation (Reveley et al., 2017; Saleem and Logothetis, 2012), thereby integrating the 3D segmentation of both cortical and subcortical regions into the same volume. This newly updated three-dimensional D99 digital brain atlas (V2.0) is intended for use as a reference standard for macaque neuroanatomical, functional, and connectional imaging studies, involving both cortical and subcortical targets. The SC21 and D99 digital templates are available as volumes and surfaces in standard NIFTI and GIFTI formats.

Sleep Power Spectral Density and Spindles in PTSD and Their Relationship to Symptom Severity.

Sleep disturbances are common in post-traumatic stress disorder (PTSD), although which sleep microarchitectural characteristics reliably classify those with and without PTSD remains equivocal. Here, we investigated sleep microarchitectural differences (i.e., spectral power, spindle activity) in trauma-exposed individuals that met (n = 45) or did not meet (n = 52) criteria for PTSD and how these differences relate to post-traumatic and related psychopathological symptoms. Using ecologically-relevant home sleep polysomnography recordings, we show that individuals with PTSD exhibit decreased beta spectral power during NREM sleep and increased fast sleep spindle peak frequencies. Contrary to prior reports, spectral power in the beta frequency range (20.31–29.88 Hz) was associated with reduced PTSD symptoms, reduced depression, anxiety and stress and greater subjective ability to regulate emotions. Increased fast frequency spindle activity was not associated with individual differences in psychopathology. Our findings may suggest an adaptive role for beta power during sleep in individuals exposed to a trauma, potentially conferring resilience. Further, we add to a growing body of evidence that spindle activity may be an important biomarker for studying PTSD pathophysiology.

Biomimetic Approaches for the Design and Fabrication of Bone-to-Soft Tissue Interfaces.

Bone-to-soft tissue interfaces are responsible for transferring loads between tissues with significantly dissimilar material properties. The examples of connective soft tissues are ligaments, tendons, and cartilages. Such natural tissue interfaces have unique microstructural properties and characteristics which avoid the abrupt transitions between two tissues and prevent formation of stress concentration at their connections. Here, we review some of the important characteristics of these natural interfaces. The native bone-to-soft tissue interfaces consist of several hierarchical levels which are formed in a highly specialized anisotropic fashion and are composed of different types of heterogeneously distributed cells. The characteristics of a natural interface can rely on two main design principles, namely by changing the local microarchitectural features (e.g., complex cell arrangements, and introducing interlocking mechanisms at the interfaces through various geometrical designs) and changing the local chemical compositions (e.g., a smooth and gradual transition in the level of mineralization). Implementing such design principles appears to be a promising approach that can be used in the design, reconstruction, and regeneration of engineered biomimetic tissue interfaces. Furthermore, prominent fabrication techniques such as additive manufacturing (AM) including 3D printing and electrospinning can be used to ease these implementation processes. Biomimetic interfaces have several biological applications, for example, to create synthetic scaffolds for osteochondral tissue repair.

Identifying structure-property relationships of micro-architectured porous scaffolds through 3D printing and finite element analysis

This study integrates 3D printing and finite element analysis (FEA) to investigate the effect of micro-architectural characteristics on the mechanical properties of porous scaffolds. The studied characteristics include the thickness of the scaffold walls and the number of domains at the cross-section. We use 3D printing to fabricate scaffolds of deliberately designed microstructures to enable strict architecture control of the scaffolds. The longitudinal compressive properties of different scaffolds are first analyzed through experimental testing. Then, FEA is conducted to investigate the mechanical properties and the deformation mechanisms of the scaffolds. We find that decreasing wall thickness leads to failure mechanism transition from wall compression failure to buckling instability. For scaffolds with different wall thicknesses, the failure mechanisms and the critical loads are evaluated using the theory of thin plate buckling. For the characteristic of the number of domains, both experimental and FEA results show increasing effective stiffness with increasing domains. Interestingly, we find that with the material properties extracted from a single wall scaffold, the computational models tend to overestimate the effective compression modulus of scaffolds with larger numbers of walls or domains than the experimental data. This observation indicates possible size-dependent material properties in 3D printed structs. Our study demonstrates that integrating experiments and computational modeling can provide fundamental insights into the mechanical properties and deformation mechanisms of micro-architectured scaffolds and unveil unique small-scale material behaviors.

Recent Advances on Stimuli-Responsive Hydrogels Based on Tissue-Derived ECMs and Their Components: Towards Improving Functionality for Tissue Engineering and Controlled Drug Delivery.

Due to their highly hydrophilic nature and compositional versatility, hydrogels have assumed a protagonic role in the development of physiologically relevant tissues for several biomedical applications, such as in vivo tissue replacement or regeneration and in vitro disease modeling. By forming interconnected polymeric networks, hydrogels can be loaded with therapeutic agents, small molecules, or cells to deliver them locally to specific tissues or act as scaffolds for hosting cellular development. Hydrogels derived from decellularized extracellular matrices (dECMs), in particular, have gained significant attention in the fields of tissue engineering and regenerative medicine due to their inherently high biomimetic capabilities and endowment of a wide variety of bioactive cues capable of directing cellular behavior. However, these hydrogels often exhibit poor mechanical stability, and their biological properties alone are not enough to direct the development of tissue constructs with functional phenotypes. This review highlights the different ways in which external stimuli (e.g., light, thermal, mechanical, electric, magnetic, and acoustic) have been employed to improve the performance of dECM-based hydrogels for tissue engineering and regenerative medicine applications. Specifically, we outline how these stimuli have been implemented to improve their mechanical stability, tune their microarchitectural characteristics, facilitate tissue morphogenesis and enable precise control of drug release profiles. The strategic coupling of the bioactive features of dECM-based hydrogels with these stimulation schemes grants considerable advances in the development of functional hydrogels for a wide variety of applications within these fields.

Counterclockwise Drilling with Different Tapered Drills Condenses the Implant Bed-An Optical Coherence Tomography In Vitro Study.

Background and Objectives: To evaluate the condensation and the microarchitecture of implant bed walls of sites prepared with counterclockwise drilling with tapered implant drills using optical coherence tomography. Materials and Methods: Four drill designs with different wall and tip angles were used. Polyurethane laminas resembling type IV bone microarchitecture were superimposed and clamped with a vice to simulate the coronal, middle, and apical aspects of the implant site. Twenty implant beds were prepared at 1200 rpm in clockwise (control) and counterclockwise (test) directions (N = 160). Optical coherence tomography (OCT) was used to evaluate the condensation and microarchitecture characteristics of the implant bed walls. The relative condensation was calculated using the Image J software Bone application. The microarchitecture was evaluated in reconstructed 3D volumes in XY, XZ, and YZ sections. Statistical analysis was performed using one-way ANOVA. Dunnet test was applied to determine differences between groups. Significance was set as p < 0.05. Results: Counterclockwise drilling (Test) condensed and changed the microarchitecture of the apical regions for all the implant beds in all of the groups when compared to clockwise drilling (control). The apical region of test groups showed the highest relative bone condensation (p = 0.026) when compared to controls. Conclusions: The direction of rotation (counterclockwise drilling) and not the design of tapered drills (tip and wall angles) is responsible for the condensation at the apical area observed in polyurethane blocks. The OCT method can be used for the evaluation of changes in density and microstructure of polyurethane blocks.

Securing Interruptible Enclaved Execution on Small Microprocessors

Computer systems often provide hardware support for isolation mechanisms such as privilege levels, virtual memory, or enclaved execution. Over the past years, several successful software-based side-channel attacks have been developed that break, or at least significantly weaken, the isolation that these mechanisms offer. Extending a processor with new architectural or micro-architectural features brings a risk of introducing new software-based side-channel attacks. This article studies the problem of extending a processor with new features without weakening the security of the isolation mechanisms that the processor offers. Our solution is heavily based on techniques from research on programming languages. More specifically, we propose to use the programming language concept of full abstraction as a general formal criterion for the security of a processor extension. We instantiate the proposed criterion to the concrete case of extending a microprocessor that supports enclaved execution with secure interruptibility. This is a very relevant instantiation, as several recent papers have shown that interruptibility of enclaves leads to a variety of software-based side-channel attacks. We propose a design for interruptible enclaves and prove that it satisfies our security criterion. We also implement the design on an open-source enclave-enabled microprocessor and evaluate the cost of our design in terms of performance and hardware size.

Understanding Fibroblast Behavior in 3D Biomaterials.

Traditional monolayer culture fails to fully recapitulate the in vivo environment of connective tissue cells such as the fibroblast. When cultured on stiff two-dimensional (2D) plastic, fibroblasts become highly proliferative forming broad lamellipodia and stress fibers. Conversely, in different three-dimensional (3D) culture systems, fibroblasts have displayed a diverse array of features; from an "activated" phenotype like that observed in 2D cultures and by myofibroblasts, to a quiescent state that likely better represents in vivo fibroblasts at rest. Today, a plethora of microfabrication techniques have made 3D culture commonplace, for both tissue engineering purposes and in the study of basic biological interactions. However, establishing the in vivo mimetic credentials of different biomimetic materials is not always straightforward, particularly in the context of fibroblast responses. Fibroblast behavior is governed by the complex interplay of biological features such as integrin binding sites, material mechanical properties that influence cellular mechanotransduction, and microarchitectural features like pore and fiber size, as well as chemical cues. Furthermore, fibroblasts are a heterogeneous group of cells with specific phenotypic traits dependent on their tissue of origin. These features have made understanding the influence of biomaterials on fibroblast behavior a challenging task. In this study, we present a review of the strategies used to investigate fibroblast behavior with a focus on the material properties that influence fibroblast activation, a process that becomes pathological in fibrotic diseases and certain cancers. Impact statement This review considers the range of materials that have been used to investigate fibroblast behavior in three-dimensional (3D) culture. It evaluates the merits of each material, the results gained, and the evolving rationale behind the presented studies. We highlight aspects of 3D culture from porosity to polarity and their varied impact on fibroblast behavior. Understanding fibroblast behavior and mechanisms of control in vitro not only serves as a direct therapeutic opportunity in diseases from cancer to fibrosis but also can facilitate progress for future regenerative therapies.

Intraskeletal consistency in patterns of vascularity within bat limb bones.

Bats are the only mammals to have achieved powered flight. A key innovation allowing for bats to conquer the skies was a forelimb modified into a flexible wing. The wing bones of bats are exceptionally long and dynamically bend with wingbeats. Bone microarchitectural features supporting these novel performance attributes are still largely unknown. The humeri and femora of bats are typically avascular, except for large-bodied taxa (e.g., pteropodid flying foxes). No thorough investigation of vascular canal regionalization and morphology has been undertaken as historically it has been difficult to reconstruct the 3D architecture of these canals. This study augments our understanding of the vascular networks supporting the bone matrix of a sample of bats (n=24) of variable body mass, representing three families (Pteropodidae [large-bodied, species=6], Phyllostomidae [medium-bodied, species=2], and Molossidae [medium-bodied, species=1]). We employed Synchrotron Radiation-based micro-Computed Tomography (SRμCT) to allow for a detailed comparison of canal morphology within humeri and femora. Results indicate that across selected bats, canal number per unit volume is similar independent of body size. Differences in canal morphometry based on body size and bone type appear primarily related to a broader distribution of the canal network as cortical volume increases. Heavier bats display a relatively rich vascular network of mostly longitudinally-oriented canals that are localized mainly to the mid-cortical and endosteal bone envelopes. Taken together, our results suggest that relative vascularity of the limb bones of heavier bats forms support for nutrient exchange in a regional pattern.

Multidimensional Mechanics of Three-Dimensional Printed and Micro-Architectured Scaffolds.

Mechanical properties of porous materials depend on their micro-architectural characteristics. Freeze casting is an effective method to fabricate micro-architectured porous scaffolds. Three key characteristics generated during freeze casting are wall thickness, number of domains at the cross-section, and transverse bridges connecting adjacent walls. To specifically study the effect of these structural characteristics on the mechanics and anisotropic compressive properties of scaffolds, we utilize additive manufacturing, i.e., 3D printing, to fabricate strictly designed cubic scaffolds with varying one characteristic at a time. We then compare strength, toughness, resilience, stiffness, and strain to failure in three orthogonal directions of the scaffolds, including longitudinal and transverse directions. To compare these multidimensional mechanics in a single diagram, we use a previously developed radar chart method to evaluate different scaffolds and unravel the effect of the structural characteristics. We find that the multidimensional mechanics can be effectively tuned by the micro-architectural characteristics. Notably, the buckling resistance of the scaffolds depends on all three structural characteristics. Our results show that an increased number of domains leads to enhanced toughness in all three directions. Increasing wall thickness leads to enhanced mechanical properties but comes at the price of losing small-sized pores, which is not favored for certain applications. In addition, adding transverse bridges increase not only the transverse strength of the scaffolds but also the longitudinal strength as they also enhance the buckling resistance. Our study provides important insights into the structure-property relationships of 3D-printed micro-architectured porous scaffolds.

Micro-architectural analysis of in-memory OLTP: Revisited

Micro-architectural behavior of traditional disk-based online transaction processing (OLTP) systems has been investigated extensively over the past couple of decades. Results show that traditional OLTP systems mostly under-utilize the available micro-architectural resources. In-memory OLTP systems, on the other hand, process all the data in main-memory and, therefore, can omit the buffer pool. Furthermore, they usually adopt more lightweight concurrency control mechanisms, cache-conscious data structures, and cleaner codebases since they are usually designed from scratch. Hence, we expect significant differences in micro-architectural behavior when running OLTP on platforms optimized for in-memory processing as opposed to disk-based database systems. In particular, we expect that in-memory systems exploit micro-architectural features such as instruction and data caches significantly better than disk-based systems. This paper sheds light on the micro-architectural behavior of in-memory database systems by analyzing and contrasting it to the behavior of disk-based systems when running OLTP workloads. The results show that, despite all the design changes, in-memory OLTP exhibits very similar micro-architectural behavior to disk-based OLTP: more than half of the execution time goes to memory stalls where instruction cache misses or the long-latency data misses from the last-level cache (LLC) are the dominant factors in the overall execution time. Even though ground-up designed in-memory systems can eliminate the instruction cache misses, the reduction in instruction stalls amplifies the impact of LLC data misses. As a result, only 30% of the CPU cycles are used to retire instructions, and 70% of the CPU cycles are wasted to stalls for both traditional disk-based and new generation in-memory OLTP.

Microengineered Materials with Self‐Healing Features for Soft Robotics

Recent advancements in soft robotics have led to the development of compliant robots that can exhibit complex motions driven by living cells, chemical reactions, or electronics. Further innovations are, however, needed to create the next generation of soft robots that can carry out advanced functions and exhibit complex locomotion. Material designs that incorporate “smart” functional properties can contribute to the development of robotic systems with in‐built mechanical responsiveness and functions. Herein, a simple material design that integrates stimuli‐responsive self‐healing and microarchitectural features to control locomotion of soft robots is reported. By employing these material designs along with hyperelastic soft actuators to control propellant dispersion and direction, a circuitry of pneumatic and microfluidic logic is created within a dragonfly‐shaped body that enables the robot to undergo user‐ and environment‐controlled locomotion over water surface. In addition to steering the robot to skim, the material properties are also leveraged to detect water acidification, temperature changes, and hydrophobic impurities such as oil. The design, fabrication, and integration strategies demonstrated herein pave a way for developing futuristic multifunctional soft robots, biomedical devices, and environmental monitoring probe.

Microarchitectural Characterization on a Mobile Workload

Geekbench is one of the most referenced cross-platform benchmarks in the mobile world. Most of its workloads are synthetic but some of them aim to simulate real-world behavior. In the mobile world, its microarchitectural behavior has been reported rarely since the hardware profiling features are limited to the public. As a popular mobile performance workload, it is hard to find Geekbench’s microarchitecture characteristics in mobile devices. In this paper, a thorough experimental study of Geekbench performance characterization is reported with detailed performance metrics. This study also identifies mobile system on chip (SoC) microarchitecture impacts, such as the cache subsystem, instruction-level parallelism, and branch performance. After the study, we could understand the bottleneck of workloads, especially in the cache sub-system. This means that the change of data set size directly impacts performance score significantly in some systems and will ruin the fairness of the CPU benchmark. In the experiment, Samsung’s Exynos9820-based platform was used as the tested device with Android Native Development Kit (NDK) built binaries. The Exynos9820 is a superscalar processor capable of dual issuing some instructions. To help performance analysis, we enable the capability to collect performance events with performance monitoring unit (PMU) registers. The PMU is a set of hardware performance counters which are built into microprocessors to store the counts of hardware-related activities. Throughout the experiment, functional and microarchitectural performance profiles were fully studied. This paper describes the details of the mobile performance studies above. In our experiment, the ARM DS5 tool was used for collecting runtime PMU profiles including OS-level performance data. After the comparative study is completed, users will understand more about the mobile architecture behavior, and this will help to evaluate which benchmark is preferable for fair performance comparison.

Bone Geometry, Density, Microstructure, and Biomechanical Properties in the Distal Tibia in Patients With Primary Hypertrophic Osteoarthropathy Assessed by Second-Generation High-Resolution Peripheral Quantitative Computed Tomography.

Periosteosis refers to pathological woven bone formation beneath the cortical bone of the long bones. It is an imaging hallmark of primary hypertrophic osteoarthropathy (PHO) and also considered as one of the major diagnostic criteria of PHO patients. Up to date, detailed information on bone quality changes in long bones of PHO patients is still missing. This study aimed to evaluate bone microarchitecture and bone strength in PHO patients by using high-resolution peripheral quantitative computed tomography (HR-pQCT). The study comprised 20 male PHO patients with the average age of 27.0 years and 20 age- and sex-matched healthy controls. The areal bone mineral density (aBMD) was assessed at the lumbar spine (L1 -L4 ) and hip (total hip and femoral neck) by dual-energy X-ray absorptiometry (DXA). Bone geometry, volumetric bone mineral density (vBMD), and microstructure parameters at the distal tibia were evaluated by using HR-pQCT. Bone strength was evaluated by finite element analysis (FEA) based on HR-pQCT screening at distal tibia. Urinary prostaglandin E2 (PGE2 ), serum phosphatase (ALP), beta-C-telopeptides of type I collagen (β-CTX), soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG), and neuronal calcitonin gene-related peptide (CGRP) were investigated. As compared with healthy controls, PHO patients had larger bone cross-sectional areas; lower total, trabecular, and cortical vBMD; compromised bone microstructures with more porous cortices, thinned trabeculae, reduced trabecular connectivity, and relatively more significant resorption of rod-like trabeculae at distal tibia. The apparent Young's modulus was significantly lower in PHO patients. The concentration of PGE2 , biomarkers of bone resorption (β-CTX and sRANKL/OPG ratio), and the neuropeptide CGRP were higher in PHO patients versus healthy controls. PGE2 level correlated negatively with vBMD and estimated bone strength and positively with bone geometry at distal tibia. The present HR-pQCT study is the first one illustrating the microarchitecture and bone strength features in long bones. © 2021 American Society for Bone and Mineral Research (ASBMR).

Differences in the microarchitectural features of the lateral collapsed lesion between osteonecrosis and subchondral insufficiency fracture of the femoral head.

Like osteonecrosis of the femoral head (ONFH), subchondral insufficiency fracture of the femoral head (SIF) causes femoral head collapse. However, little is known about the differences between the two diseases regarding the morphological features of the collapsed lesion. We tested the hypothesis that the morphological features of the lateral collapsed lesion would differ between ONFH and SIF. Twenty femoral heads histopathologically diagnosed as ONFH (n=10) or SIF (n=10) were used in this study. In the lateral collapsed lesion of each femoral head, cubic regions of interest (ROIs) were selected within the collapsed subchondral area and the nearby non-collapsed subchondral area. Micro-CT-based microarchitectural parameters were compared between the ROIs in each disease. Additionally, correlations between histopathological and microarchitectural features were evaluated. In ONFH, bone volume fraction, trabecular thickness, and bone mineral density in the collapsed area were all significantly lower than those in the nearby non-collapsed area where thickened bone trabeculae accompanied by appositional bone formation were invariably seen. On the other hand, in SIF there were no significant differences between the ROIs in any of these microarchitectural parameters. Histopathologically, varying degrees of callus formation overlying the fracture of the subchondral plate were seen around the lateral collapsed lesion. The morphological features of the lateral collapsed lesion were inconsistent between ONFH and SIF, suggesting different pathomechanisms of femoral head collapse.

Large negative lymph nodes – a surrogate for immune activation in rectal cancer patients?

AimThe size of regional, tumor draining lymph nodes without metastasis (LNneg) found in rectal cancer resection specimens varies and seems to be related to patient survival. Yet, the histopathological features influencing LNneg size in rectal cancer have not been studied in detail. Our pilot study focused on investigating the relationship between lymph node (LN) size and LNneg microarchitecture in rectal cancer (RC) resection specimens. MethodIn this retrospective cohort study, resection specimens from 146 RC patients, treated with either surgery alone (n = 29) or neoadjuvant therapy followed by resection (n = 117), were included in the study. Histology of LNnegs was reviewed to establish number of lymphoid follicles and presence of intranodal fat. Longest long axis and area of each LN were measured digitally. Results1830 LNnegs were measured. The microarchitecture was analyzed in a subset of 680 LNnegs. 153 (22.5 %) LNnegs contained intranodal fat. After neoadjuvant treatment, presence of intranodal fat was related to smaller LNneg area (median (range) area of LNneg without intranodal fat: 4.51 mm2 (0.15-46.89 mm2), with intranodal fat: 3.46 mm2 (0.12-27.22 mm2), p = 0.048). A higher number of lymphoid follicles was related to a larger LNneg area in both patient groups (p < 0.001). ConclusionOur pilot data suggest that in rectal cancer the presence of large regional LNnegs may reflect increased immune activation due to tumor related antigens. Further studies are warranted to investigate whether histologically visible microarchitectural features of LNnegs such as lymphoid follicles translate to particular features in radiological images and hence could potentially help to identify LNneg with more certainty at the time of pre-treatment disease staging.

Sacrificial Fibers Improve Matrix Distribution and Micromechanical Properties in a Tissue-Engineered Intervertebral Disc

Tissue-engineered replacement discs are an area of intense investigation for the treatment of end-stage intervertebral disc (IVD) degeneration. These living implants can integrate into the IVD space and recapitulate native motion segment function. We recently developed a multiphasic tissue-engineered disc-like angle-ply structure (DAPS) that models the micro-architectural and functional features of native tissue. While these implants resulted in functional restoration of the motion segment in rat and caprine models, we also noted deficiencies in cell infiltration and homogeneity of matrix deposition in the electrospun poly(ε-caprolactone) outer region (annulus fibrosus, AF) of the DAPS. To address this limitation, here, we incorporated a sacrificial water-soluble polymer, polyethylene oxide (PEO), as a second fiber fraction within the AF region to increase porosity of the implant. Maturation of these PEO-modified DAPS were evaluated after 5 and 10 weeks of in vitro culture in terms of AF biochemical content, MRI T2 values, overall construct mechanical properties, AF micromechanical properties and cell and matrix distribution. To assess the performance of the PEO-modified DAPS in vivo, precultured constructs were implanted into the rat caudal IVD space for 10 weeks. Results showed that matrix distribution was more homogenous in PCL/PEO DAPS, as evidenced by more robust histological staining, organized collagen deposition and micromechanical properties, compared to standard PCL-only DAPS in vitro. Cell and matrix infiltration were also improved in vivo, but no differences in macromechanical properties and a trend towards improved micromechanical properties were observed. These findings demonstrate that the inclusion of a sacrificial PEO fiber fraction in the DAPS AF region improves cellular colonization, matrix elaboration, and in vitro and in vivo function of an engineered IVD implant. Statement of significanceThis work establishes a method for improving cell infiltration and matrix distribution within tissue-engineered dense fibrous scaffolds for intervertebral disc replacement. Tissue-engineered whole disc replacements are an attractive alternative to the current gold standard (mechanical disc arthroplasty or vertebral fusion) for the clinical treatment of patients with advanced disc degeneration.

MON-382 Bone Quality and Strength in Obese Men with Type 2 Diabetes Mellitus Are Impaired and Negatively Influenced by Adiposity

Background: Obesity and type 2 diabetes mellitus (T2DM) are both associated with normal to above average bone mineral density (BMD) but increased risk of fragility fractures. The impact of T2DM on bone mechanical and microarchitectural features in the obese population is unknown. We hypothesize that obese diabetics have lower bone quality compared to obese nondiabetic individuals. In this study, we investigated the microarchitectural features and mechanical properties of bone of obese men with and without T2DM along with the independent predictors of bone strength. Methods: Ninety-seven obese men (BMI >30) aged 35-65 years-old of which 38 had T2DM were included in the analysis. BMD and body composition were evaluated by DXA and bone microarchitecture of the tibia by high-resolution peripheral quantitative computed tomography. Bone strength was assessed by micro finite element analysis-derived parameters as failure load (f. load) and stiffness. Serum testosterone and estradiol were measured by LC-MS. Serum SHBG, osteocalcin (OCN), C-telopeptide (CTx) and sclerostin (SCL) were measured by ELISA. Results: OCN is lower in obese men with T2DM compared to those without T2DM (4.8 ± 2.8 vs 6.2 ± 2.6 ng/mL p=0.03, respectively), with also a trend for reduced CTx and SCL in the former. BMD at all sites was reduced in obese men with T2DM, but there were no differences in body composition. Obese diabetics also had lower tibial total volumetric BMD (vBMD) (p=0.04) and trabecular vBMD (p=0.01) with greater trabecular spacing (p=0.005). F. load (13.3 ± 2.1 vs 14.5 ± 2.3 kN, p= 0.02) and stiffness (24.7± 4.2 vs 27 ± 4.6 kN/mm, p=0.02) were reduced in men with T2DM relative to men without T2DM, respectively. F. load and stiffness were positively correlated with BMD at all sites, fat free mass (FFM), lean mass, free testosterone, free estradiol and SCL, but negatively correlated with % total body fat and visceral adipose tissue (VAT). FFM, BMD of the total hip, femoral neck and lumbar spine and free testosterone were significant independent predictors of bone strength in the entire group (model: R2: 65.01 p< 0.0001 for f. load and model: R2:63.21 p < 0.0001 for stiffness), whereas age and lumbar spine BMD were found to be independent predictors of bone strength in the non-diabetic group (model R2: 54.6 p< 0.0001 for both f. load and stiffness). Analysis limited to the diabetic subgroup showed that BMD at the femoral neck and total hip, % total body fat, VAT volume, SCL and free estradiol were independent predictors of bone strength (model: R2: 88.4 and p< 0.0001 for f. load and model: R2: 85.3 and p<0.0001 for stiffness). Interleukin-6 was comparable between groups. Conclusions: Obese men with T2DM have lower bone formation and impaired bone quality and strength compared to those without T2DM. In addition to BMD and gonadal hormones, adiposity is an important predictor of bone strength in obese men with T2DM.

SUN-LB69 A Comparison Between Weight Loss Associated Bone Loss From Lifestyle Measures Versus Bariatric Surgery

Background Despite improvement in many metabolic outcomes, bone loss remains a concern with weight loss (WL). In this prospective study, we compared the effects of WL from lifestyle intervention (LI) and bariatric surgery (BS) on WL-associated bone loss. We hypothesize that the higher WL from bariatric surgery will result in a greater decline in bone mineral density (BMD) and bone quality. Methods Twenty-nine obese subjects (BMI > 30 kg/m2; weight: 107±19.3 kg) were included in the study; 13 participated in a LI study of WL (supervised diet+exercise) and 16 underwent BS. Assessments were done at 10% WL and at 6 months. Areal BMD and body composition were evaluated by DXA; bone micro-architecture and bone strength by microfinite element analysis-derived parameters as failure load (f.load) and stiffness at the distal radius and distal tibia were evaluated by high resolution peripheral quantitative computed tomography. Serum bone turnover markers, adipokines and cytokines were measured by Elisa. Results Participants in the LI arm were significantly older (71.3±4 vs 48.2±10 y.o., p < 0.001) and lighter (93.4 ± 8 vs. 118.5±18 kg, P=0.001) compared to the BS arm. Analysis adjusted for baseline age and weight showed no significant differences in areal BMD at all sites, volumetric BMD and bone microarchitectural features of the radius and tibia, except for higher cortical porosity (Ct.Po) at the tibia in the LI arm compared to the BS arm (3.0±0.3 vs 1.7±0.3%, p=0.04, respectively). The average WL at 6 months were -11.87±4.7 vs.-15.96±5.1%, p=0.07, for LI and BS, respectively. At 10%WL, the LI arm had a reduction in trabecular volumetric BMD (tb.vBMD) at the radius (-2.2±1.2 vs. 3.1±4.8% P=0.05) and tibia (-2.2±1.4 vs. 2.2±3.9 % P=0.02, respectively) compared to BS arm which had increases in this parameter. There was also a trend for reduced radius trabecular number and thickness in the LI arm at 10% WL. Meanwhile, there was a trend for reduction in total hip BMD, f.load and stiffness at the radius in the BS arm only. At 6 months, tb.vBMD at the radius was reduced in LI (-2.7±0.9%) relative to the increase in BS group (5.7±2.0%), p=0.008. There was a reduction in F.load (-5.3±2.4 vs 0.6±1.2%, p=0.09) and stiffness (-6.1±2.7 vs. 0.8±1.4%, p=0.08) of borderline significance at the tibia in the BS compared to no change in LI arm. BS arm showed a greater increase in serum C- telopeptide (28.1±48 vs. 81.3±30%, P=<0.05), an index of bone resorption, and in adiponectin (-0.7±8 vs.36.2±22.1%, P=0.01) compared to LI at 6 months. There were no significant differences in changes in lean and fat mass at 6 months in both arms. Conclusion: Although WL from LI resulted in reduced radial tb.vBMD, BS was associated with a greater increase in bone resorption and a trend for reduction in bone strength at the weight-bearing tibia at 6 months compared to LI. Results from this pilot project need confirmation in a larger study with longer duration of follow-up.