Relationships between radiographic parameters and spinopelvic muscles in adult spinal deformity patients.

INTRODUCTION: While the clinical impact of coronal and sagittal alignment in adult spinal deformity (ASD) patients (pts) is established, there is a paucity of data in terms of axial plane deformity and potential association between muscle degeneration and 3D deformity. The purpose of this study was to analyze spinopelvic muscles characteristics in association with the 3D deformity of ASD patients. METHODS: This is a prospective cohort study; primary lumbar scoliosis patients (Cobb > 20°) were enrolled and sustained a low-dose X-rays with 3D spinal reconstructions and a fat/water separation MRI (from C7 to the knee). Volumetric 3D reconstructions and fat infiltration (FI) of 6 muscles groups were performed. Relationships between muscular data, radiographic parameters and health-related quality of life were investigated. Patients were stratified and compared based on the SRS classification, the odontoid-hip axis (ODHA) angle (> or < 6.1°) and occurrence of rotatory subluxation. RESULTS AND DISCUSSION: Twenty-eight patients were enrolled with a mean age of 60 ± 16yo and mean body mass index of 26 ± 4 kg/m2 without differences between groups. There were a moderate sagittal malalignment and a Cobb angle of 45 ± 11° (table). Muscular volume was smaller in patients with more severe deformity (p > 0.05). Pts with ODHA > 6.1° or pelvic incidence minus lumbar lordosis > 10° had significantly higher FI for the 6 muscular groups, patients with pelvic tilt > 20° had significantly higher FI for erector spinae, hip flexors and extensors (p < 0.05). SF36-PCS significantly correlated with the muscular volume; SRS and Oswestry disability index correlated with the erectors spinae volume (p < 0.05). CONCLUSION: This study analyzed for the first time the relationship between 3D radiographic parameters and muscular characteristics in ASD. Sagittal malalignment is associated with increased FI and decreased muscle volumes with poor outcomes. These slides can be retrieved under Electronic Supplementary Material.

Synthesized tissue-equivalent dielectric phantoms using salt and polyvinylpyrrolidone solutions.

PURPOSE: To explore the use of polyvinylpyrrolidone (PVP) for simulated materials with tissue-equivalent dielectric properties. METHODS: PVP and salt were used to control, respectively, relative permittivity and electrical conductivity in a collection of 63 samples with a range of solute concentrations. Their dielectric properties were measured with a commercial probe and fitted to a 3D polynomial in order to establish an empirical recipe. The material's thermal properties and MR spectra were measured. RESULTS: The empirical polynomial recipe (available at https://www.amri.ninds.nih.gov/cgi-bin/phantomrecipe) provides the PVP and salt concentrations required for dielectric materials with permittivity and electrical conductivity values between approximately 45 and 78, and 0.1 to 2 siemens per meter, respectively, from 50 MHz to 4.5 GHz. The second- (solute concentrations) and seventh- (frequency) order polynomial recipe provided less than 2.5% relative error between the measured and target properties. PVP side peaks in the spectra were minor and unaffected by temperature changes. CONCLUSION: PVP-based phantoms are easy to prepare and nontoxic, and their semitransparency makes air bubbles easy to identify. The polymer can be used to create simulated material with a range of dielectric properties, negligible spectral side peaks, and long T2 relaxation time, which are favorable in many MR applications. Magn Reson Med 80:413-419, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

3D configuration of mandibles and controlling muscles in rove beetles based on micro-CT technique.

X-ray micro-CT is a powerful tool to visualize without damage details of the inner structures of beetles, the largest order of insects with a hard external skeleton. This contribution shows the three-dimensional (3D) reconstruction of the head morphology of three rove beetle species (Insecta, Coleoptera, Staphylinidae)--Noddia sp., Creophilus maxillosus, and Hesperosoma sp.--using X-ray microtomography at a spatial resolution of 6 µm. The details of skeletal muscle fiber insertions are described, giving a comprehensive overview of mandible mobility and organization. With the support of 3D rendering, we discuss the relationship among the mandible forms, the development of the muscles controlling the movement, and the head morphology. The well-developed posterior part of the head capsule is always accompanied by a well-developed mandible, a large adductor muscle, and a large apodeme for the wide areas of the muscle fiber attachment. In Noddia sp., muscles connected to the posterolateral angle of the head capsule are mainly short muscles, whereas in Creophilus maxillosus, the latter are mainly long muscles, and in Hesperosoma sp. no mandible adductor muscle fibers are present on the posterolateral angle of the head capsule. These results offer new invaluable information regarding the biting functions of beetle mandibles and the trend of their morphological change during their long-term evolution.

Evaluation of a conducting elastomeric composite material for intramuscular electrode application.

Electrical stimulation of the muscle has been proven efficacious in preventing atrophy and/or reanimating paralyzed muscles. Intramuscular electrodes made from metals have significantly higher Young's Moduli than the muscle tissues, which has the potential to cause chronic inflammation and decrease device performance. Here, we present an intramuscular electrode made from an elastomeric conducting polymer composite consisting of PEDOT-PEG copolymer, silicone and carbon nanotubes (CNT) with fluorosilicone insulation. The electrode wire has a Young's modulus of 804 (±99) kPa, which better mimics the muscle tissue modulus than conventional stainless steel (SS) electrodes. Additionally, the non-metallic composition enables metal-artifact free CT and MR imaging. These soft wire (SW) electrodes present comparable electrical impedance to SS electrodes of similar geometric surface area, activate muscle at a lower threshold, and maintain stable electrical properties in vivo up to 4 weeks. Histologically, the SW electrodes elicited significantly less fibrotic encapsulation and less IBA-1 positive macrophage accumulation than the SS electrodes at one and three months. Further phenotyping the macrophages with the iNOS (pro-inflammatory) and ARG-1 (pro-healing) markers revealed significantly less presence of pro-inflammatory macrophage around SW implants at one month. By three months, there was a significant increase in pro-healing macrophages (ARG-1) around the SW implants but not around the SS implants. Furthermore, a larger number of AchR clusters closer to SW implants were found at both time points compared to SS implants. These results suggest that a softer implant encourages a more intimate and healthier electrode-tissue interface. STATEMENT OF SIGNIFICANCE: Intramuscular electrodes made from metals have significantly higher Young's Moduli than the muscle tissues, which has the potential to cause chronic inflammation and decrease device performance. Here, we present an intramuscular electrode made from an elastomeric conducting polymer composite consisting of PEDOT-PEG copolymer, silicone and carbon nanotubes with fluorosilicone insulation. This elastomeric composite results in an electrode wire with a Young's modulus mimicking that of the muscle tissue, which elicits significantly less foreign body response compared to stainless steel wires. The lack of metal in this composite also enables metal-artifact free MRI and CT imaging.

Fluoro-deoxy-glucose uptake in the mylohyoid muscle: a common misconception.

AIM: The mylohyoid muscle is often believed to exhibit high physiologic fluoro-deoxy-glucose (FDG) uptake. Aim of this study was to use PET/MR for adequately assessing the normal FDG distribution in floor of the mouth (FOM) muscles and neighboring major salivary glands. MATERIALS AND METHODS: Patients scanned with a simultaneous PET/MRI system for initial staging or follow-up of head and neck tumors, with no malignant lesions in salivary glands or in FOM, were included. Volumes-of-interest (VOIs) were positioned separately for bilateral mylohyoid, digastric, genioglossus, and geniohyoid muscles, based on T2-weighted and T1-weighted images, and for bilateral parotid, submandibular, and sublingual glands in the same way. SUVmax was measured for each VOI. RESULTS: Six hundred and ninety-two VOIs were positioned. FDG uptake in mylohyoid (SUVmax = 1.94 ± 0.37) and digastric muscles (SUVmax = 2.01 ± 0.37) were significantly higher compared to that in geniohyoid (SUVmax = 1.67 ± 0.53) and genioglossus muscles (SUVmax = 1.75 ± 0.54) (Friedman's test; P < 0.001). FDG uptake in the sublingual glands (SUVmax = 3.77 ± 1.63) was significantly higher compared to the parotid glands (SUVmax = 2.34 ± 0.60) and submandibular glands (SUVmax = 2.51 ± 0.59) (Wilcoxon signed-ranks test; P < 0.001). FDG uptake in sublingual glands was significantly higher than FDG uptake in the mylohyoid muscles (P < 0.001). FDG uptake in the parotid, submandibular, and sublingual glands was inversely correlated to the age of subjects (Spearman' rho coefficient: -0.397/P = 0.004; -0.329/P = 0.021; -0.535/P < 0.001, respectively). CONCLUSION: The sublingual glands yield the highest physiologic FDG uptake in the FOM. High FDG uptake in the mylohyoid muscle is a common misconception.

Comparative morphology of cheliceral muscles using high-resolution X-ray microcomputed-tomography in palpimanoid spiders (Araneae, Palpimanoidea).

Spiders are important predators in terrestrial ecosystems, yet we know very little about the principal feeding structures of spiders, the chelicerae, which are functionally equivalent to "jaws" or "mandibles" and are an extremely important aspect of spider biology. In particular, members of Palpimanoidea have evolved highly unusual cheliceral morphologies and functions, including high-speed, ballistic movements in mecysmaucheniid spiders, the fastest arachnid movements known thus far, and the elongated, highly maneuverable chelicerae of archaeids that use an attack-at-a-distance strategy. Here, using micro-Computed-Tomography scanning techniques, we perform a comparative study to examine cheliceral muscle morphology in six different spider specimens representing five palpimanoid families. We provide a hypothesis for homology in palpimanoid cheliceral muscles and then compare and contrast these findings with previous studies on other non-palpimanoid spiders. We document and discuss two sets of cheliceral muscles in palpimanoids that have not been previously observed in other spiders or which may represent a position shift compared to other spiders. In the palpimanoids, Palpimanus sp., Huttonia sp., and Colopea sp. showed similar cheliceral muscle anatomy. In Eriauchenius ranavalona, which has highly maneuverable chelicerae, some of the muscles have a more horizontal orientation, and there is a greater degree of cheliceral muscle divergence. In Zearchaea sp. and Aotearoa magna, some muscles have also shifted to a more horizontal orientation, and in Zearchaea sp., a species with a ballistic, high-speed predatory strike, there is a loss of cheliceral muscles. This research is a first step toward understanding cheliceral form and function across spiders.

Optical Redox Imaging of Fixed Unstained Muscle Slides Reveals Useful Biological Information.

PURPOSE: Optical redox imaging (ORI) technique images cellular autofluorescence of nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp containing FAD, i.e., flavin adenine dinucleotide). ORI has found wide applications in the study of cellular energetics and metabolism and may potentially assist in disease diagnosis and prognosis. Fixed tissues have been reported to exhibit autofluorescence with similar spectral characteristics to those of NADH and Fp. However, few studies report on quantitative ORI of formalin-fixed paraffin-embedded (FFPE) unstained tissue slides for disease biomarkers. We investigate whether ORI of FFPE unstained skeletal muscle slides may provide relevant quantitative biological information. PROCEDURES: Living mouse muscle fibers and frozen and FFPE mouse muscle slides were subjected to ORI. Living mouse muscle fibers were imaged ex vivo before and after paraformaldehyde fixation. FFPE muscle slides of three mouse groups (young, mid-age, and muscle-specific overexpression of nicotinamide phosphoribosyltransferase (Nampt) transgenic mid-age) were imaged and compared to detect age-related redox differences. RESULTS: We observed that living muscle fiber and frozen and FFPE slides all had strong autofluorescence signals in the NADH and Fp channels. Paraformaldehyde fixation resulted in a significant increase in the redox ratio Fp/(NADH + Fp) of muscle fibers. Quantitative image analysis on FFPE unstained slides showed that mid-age gastrocnemius muscles had stronger NADH and Fp signals than young muscles. Gastrocnemius muscles from mid-age Nampt mice had lower NADH compared to age-matched controls, but had higher Fp than young controls. Soleus muscles had the same trend of change and appeared to be more oxidative than gastrocnemius muscles. Differential NADH and Fp signals were found between gastrocnemius and soleus muscles within both mid-aged control and Nampt groups. CONCLUSION: Aging effect on redox status quantified by ORI of FFPE unstained muscle slides was reported for the first time. Quantitative information from ORI of FFPE unstained slides may be useful for biomedical applications.

The complex trophic anatomy of silver carp, Hypophthalmichthys molitrix, highlighting a novel type of epibranchial organ.

Hypophthalmichthys molitrix, silver carp, is an invasive Asian carp that has become increasingly widespread and ecologically destructive within the upper Mississippi River Basin. Its complex trophic anatomy may help explain the apparent efficiency with which they consume phytoplankton, outcompeting native filter feeders. This cypriniform species is characterized by trophic synapomorphies that include a palatal organ, loss of upper pharyngeal jaws, and a hypertrophied lower pharyngeal jaw. However, in silver carp these structures have become greatly modified and diverge from the more basal condition that characterizes species such as goldfish. The trophic apparatus of silver carp is composed of discrete structures that are functionally coupled: filtering plates, paired epibranchial organs (EBO), a modified palatal organ composed of large muscular folds that interdigitate with the filtering plates, and hypertrophied lower pharyngeal jaws and teeth. The filtering plates fill a significant portion of the buccal cavity, especially since the distal parts of these filtering plates make up a key component of the EBOs. EBOs, food aggregating structures found in many teleosts, are thought to have independently evolved at least six times. Ranging in complexity from small slits on the dorsal wall of the pharyngeal cavity to exceedingly intricate spiraling structures, EBOs are morphologically diverse among filter-feeding fishes. Despite this morphological diversity and broad taxonomic distribution, little is known regarding the functional anatomy of the EBO. Moreover, the EBO in silver carp is distinct from the organs previously described in other species, being created by four independent pharyngeal involutions (instead of the more typical one or two) that form spiral-shaped pharyngeal tubes surrounded by circumferential muscle. On each side of the head greatly hypertrophied hyomandibulae and opercles are connected to the anterior cartilaginous caps of the bilateral EBOs via enlarged muscles. Given that these fish are pump filter feeders we hypothesize that the opercula may compress and expand the EBOs during pumping causing food to be moved posteriorly toward the pharyngeal jaws.

Three-dimensional temporomandibular joint muscle attachment morphometry and its impacts on musculoskeletal modeling.

In musculoskeletal models of the human temporomandibular joint (TMJ), muscles are typically represented by force vectors that connect approximate muscle origin and insertion centroids (centroid-to-centroid force vectors). This simplification assumes equivalent moment arms and muscle lengths for all fibers within a muscle even with complex geometry and may result in inaccurate estimations of muscle force and joint loading. The objectives of this study were to quantify the three-dimensional (3D) human TMJ muscle attachment morphometry and examine its impact on TMJ mechanics. 3D muscle attachment surfaces of temporalis, masseter, lateral pterygoid, and medial pterygoid muscles of human cadaveric heads were generated by co-registering measured attachment boundaries with underlying skull models created from cone-beam computerized tomography (CBCT) images. A bounding box technique was used to quantify 3D muscle attachment size, shape, location, and orientation. Musculoskeletal models of the mandible were then developed and validated to assess the impact of 3D muscle attachment morphometry on joint loading during jaw maximal open-close. The 3D morphometry revealed that muscle lengths and moment arms of temporalis and masseter muscles varied substantially among muscle fibers. The values calculated from the centroid-to-centroid model were significantly different from those calculated using the 'Distributed model', which considered crucial 3D muscle attachment morphometry. Consequently, joint loading was underestimated by more than 50% in the centroid-to-centroid model. Therefore, it is necessary to consider 3D muscle attachment morphometry, especially for muscles with broad attachments, in TMJ musculoskeletal models to precisely quantify the joint mechanical environment critical for understanding TMJ function and mechanobiology.

Brominated radiopaque liposomes: contrast agent for computed tomography of liver and spleen: a preliminary report.

Contrast enhancement of liver and spleen in the dog was obtained after intravenous administration of brominated radioopaque liposomes (ROL) (1-5 micron in diameter. Computed tomographic (CT) numbers generated before and after 3 hours of ROL administration demonstrated an increase in hepatic attenuation. ROL are biodegradable lipid vesicles that can be subjected to further physicochemical modifications (size, charge composition) that alter their biodistribution and pharmacokinetics. These changes can result in improved hepatosplenic contrast enhancement.

Polyacrylamide-based phantoms as tissue substitute in experimental radiation physics.

Polyacrylamide-based tissue-equivalent phantoms simulating cortical bone and muscle are described. The equivalency is based upon similar elemental composition and density, and partial similarity in the morphology of bone. Satisfactory results were obtained when the phantoms were tested at low (20 keV) and high (15 MeV) gamma radiation. Applicability of this phantom material to neutron transport is discussed. The material can be molded and shaped and its composition is easily modified by altering the proportions of the constituents. Trace elements or radionuclides are easily added. Details of the physical and radiation characteristics of the formulated systems are given together with the manufacturing procedures.

[Demonstration of non-metallic foreign bodies by conventional x-ray techniques and computer tomography. Absorption coefficient of glass, plastic and wood (author's transl)]. / Nachweisbarkeit von nicht-metallischen Fremdkörpern durch konventionelle Röntgentechnik und Computertomographie. Strahlenabsorptionskoeffizienten von Glas, Kunststoff und Holz.

Densitometric measurements were carried out on various types of glass, plastic and wood in order to determine the scope of computer tomography in detecting nonmetallic foreign bodies. CT was superior to conventional film techniques for localising glass when situated near bone. Densitometry of plastic materials showed wide variation of these substances and the results hae been tabulated. Heavy polymers exceeded +200 H, light synthetic materials were between 0 and -100 H. Computer tomographic absorption measurements of wood showed that the density depended on its water content. Measurements of different types of wood, with different degrees of hydration, showed that changes in density could be brought about by incorporation of fluid into the wood.

Vascular anatomy of the upper extremity muscles.

This study delineates the vascular anatomy of the upper extremity with particular attention toward the size, location, and number of vascular pedicles supplying each muscle. Ten cadaver upper extremities were dissected. A total of 440 muscles and 2209 pedicles were identified. The major "named" arterial source, number of pedicles, and pattern of perfusion for each muscle were delineated. Detailed description of the vascular anatomy of muscles commonly used for tendon transfer and local flaps is presented. The potential use of the coracobrachialis flap for contouring the infraclavicular area is elucidated. The anatomic bases of the anconeus and flexor carpi ulnaris flaps are confirmed. The radial and ulnar arteries may be used as microvascular donor or recipient vessels without compromising forearm muscle perfusion.

Clinical evaluation of poor performance in the racehorse: the results of 275 evaluations.

A clinical sports medicine evaluation was applied to 275 racehorses with a history of poor racing performance. The poor performance evaluation included a) general physical examination and basic laboratory screening; b) respiratory examination including auscultation, thoracic radiographs, ventilation-perfusion lung scintigraphy and upper airway endoscopy at rest and during maximal treadmill exercise c) examination of the musculoskeletal system including lameness examination, video gait analysis at high speed, post exercise serum chemistry to identify obvious as well as sub-clinical myopathies, high detail radiography and nuclear scintigraphy; d) cardiac examination including auscultation, electrocardiographic analysis during strenuous exercise and when indicated, echocardiography; and e) a standardised exercise stress test entailing the measurement of oxygen consumption, carbon dioxide production, venous blood lactate concentration and heart rate during sequentially increasing running speeds on the high speed treadmill. The choice of diagnostic methodologies utilised were tailored to each individual in order to determine most efficiently the abnormalities contributing to inadequate racing performance. The results of this clinical evaluation showed that 1) many of the diagnoses were subtle requiring the use of sophisticated diagnostic equipment including scintigraphy and dynamic evaluation of the horse exercising on the high speed treadmill and 2) 84 per cent of the horses were diagnosed as suffering from more than one problem leading to the supposition that inadequate athletic performance is often caused by a constellation of abnormalities requiring a comprehensive approach to diagnosing decreased athletic capability.

Structure and mechanical properties of Octopus vulgaris suckers.

In this study, we investigate the morphology and mechanical features of Octopus vulgaris suckers, which may serve as a model for the creation of a new generation of attachment devices. Octopus suckers attach to a wide range of substrates in wet conditions, including rough surfaces. This amazing feature is made possible by the sucker's tissues, which are pliable to the substrate profile. Previous studies have described a peculiar internal structure that plays a fundamental role in the attachment and detachment processes of the sucker. In this work, we present a mechanical characterization of the tissues involved in the attachment process, which was performed using microindentation tests. We evaluated the elasticity modulus and viscoelastic parameters of the natural tissues (E ∼ 10 kPa) and measured the mechanical properties of some artificial materials that have previously been used in soft robotics. Such a comparison of biological prototypes and artificial material that mimics octopus-sucker tissue is crucial for the design of innovative artificial suction cups for use in wet environments. We conclude that the properties of the common elastomers that are generally used in soft robotics are quite dissimilar to the properties of biological suckers.

A 3D interactive model and atlas of the jaw musculature of Alligator mississippiensis.

Modern imaging and dissemination methods enable morphologists to share complex, three-dimensional (3D) data in ways not previously possible. Here we present a 3D interactive model of the jaw musculature of the American Alligator (Alligator mississippiensis). Alligator and crocodylian jaw musculature is notoriously challenging to inspect and interpret because of the derived nature of the feeding apparatus. Using Iodine-contrast enhanced microCT imaging, a segmented model of jaw muscles, trigeminal nerve, brain and skull are presented as a cross-sectional atlas and 3D, interactive pdf of the rendered model. Modern 3D dissemination methods like this 3D Alligator hold great potential for morphologists to share anatomical information to scientists, educators, and the public in an easily downloadable format.

Hounsfield Units ranges in CT-scans of bog bodies and mummies.

Mummification processes, either artificial or natural, preserve the tissues from postmortem decay, but change them from their original state. In this study we provided the first comprehensive set of Hounsfield Unit (HU) ranges specific for tissues mummified under different environmental conditions (peat bog, cold-dry and hot-dry environment). We also analyzed the impact of different museal preservation techniques on the HU ranges, as e.g. in the Tollund Man and Grauballe Man, two bog bodies from Denmark. The HU results for mummies were compared with HU results from forensic cases, cremated and inhumated ancient human skeletal remains, and fossil animal bones. Knowledge of the typical HU range for the different tissues in mummies may help to avoid misinterpretation of increased or reduced radiodensity as evidence of paleopathological conditions. Finally, we demonstrate the practical benefit of using our re-defined HU ranges by showing the improved results of 3D visualization from automatic segmentation in an Inca mummy from Mount Llullaillaco.

X-ray diffraction enhanced imaging as a novel method to visualize low-density scaffolds in soft tissue engineering.

Scaffold visualization is challenging yet essential to the success of various tissue engineering applications. The aim of this study was to explore the potential of X-ray diffraction enhanced imaging (DEI) as a novel method for the visualization of low density engineered scaffolds in soft tissue. Imaging of the scaffolds made from poly(L-lactide) (PLLA) and chitosan was conducted using synchrotron radiation-based radiography, in-line phase-contrast imaging (in-line PCI), and DEI techniques as well as laboratory-based radiography. Scaffolds were visualized in air, water, and rat muscle tissue. Compared with the images from X-ray radiography and in-line PCI techniques, DEI images more clearly show the structure of the low density scaffold in air and have enhanced image contrast. DEI was the only technique able to visualize scaffolds embedded in unstained muscle tissue; this method could also define the microstructure of muscle tissue in the boundary areas. At a photon energy of 20 KeV, DEI had the capacity to image PLLA/chitosan scaffolds in soft tissue with a sample thickness of up to 4 cm. The DEI technique can be applied at high X-ray energies, thus facilitating lower in vivo radiation doses to tissues during imaging as compared to conventional radiography.

Calcium phosphates compounds in conjunction with hydrogel as carrier for BMP-2: a study on ectopic bone formation in rats.

Current treatment of fractures often involves the use of bone graft or bone morphogenetic proteins (BMP) to induce fracture healing, especially in patients with a compromised healing capacity. BMP has to be delivered in conjunction with a carrier. Unfortunately, there are drawbacks and limitations with current carriers, including their bovine origin which carries the risk of an immunological response. The physical properties also limit the use to open surgical procedures, as it cannot be injected. New carriers with improved properties are therefore needed. The aim of this study was to assess the ectopic bone forming capability of various calcium phosphate compounds when used in conjunction with a hydrogel as the carrier for BMP-2. Five different ceramic additives were tested, including ß-tricalcium phosphate and four types of hydroxyapatite (HAP) (nanoHAP, HAP, clods of HAP >100 µm, and the biomimetic HAP Ostim35®). The compounds were injected into the thigh muscle of rats, where it formed a gel in situ. After 4 weeks bone formation was evaluated by peripheral quantitative computed tomography and histology. The major finding was that the 20 nm nanoHAP yielded a higher bone density than the other additives (P=0.0008, ANOVA with Tukey's multiple comparison test). We hypothesize that the higher bone density induced by nanoHAP might be due to nanocrystals of calcium phosphate acting as direct building blocks for biomineralization.