Comparison of the mechanical properties and anchoring performance of polyvinylidene fluoride and polypropylene barbed sutures for tendon repair.

Polyvinylidene fluoride (PVDF) has been considered as an alternative suture material to replace polypropylene (PP) due to its superior biocompatibility and mechanical properties, but it has never been examined for use in barbed sutures, particularly for tendon repair. This study fabricated size 2-0 PVDF and PP bidirectional barbed sutures and compared their mechanical properties and anchoring performance in patellar tendons. The mechanical properties were evaluated via tensile testing, and the anchoring performance of the barbed sutures was assessed by a tendon suture pullout test. Sixty porcine patellar tendons were harvested, transected to mimic a full-thickness injury, and repaired using a cross-locked cruciate suturing technique. The ultimate tensile force was 60% higher for the PVDF barbed sutures (22.4 ± 2.1 N) than for the PP barbed sutures (14.0 ± 1.7 N). The maximum pullout force was 35% higher for PVDF barbed sutures (70.8 ± 7.8 N) than for PP barbed sutures (52.4 ± 5.8 N). The force needed to form a 2-mm gap, indicative of repair failure, was similar between the PVDF (29.2 ± 5.0 N) and PP (25.6 ± 3.1 N) barbed sutures, but both were greater than the 2-mm-gap forces for non-barbed sutures of the same size. In this study, PVDF barbed sutures provided better mechanical properties and improved tissue anchoring performance compared to the barbed PP sutures for porcine patellar tendon repair, demonstrating that PVDF monofilament sutures can be barbed and used effectively for tendon repair.

Location of brachial plexus birth injury affects functional outcomes in a rat model.

Brachial plexus birth injury (BPBI) results in shoulder and elbow paralysis with shoulder internal rotation and elbow flexion contracture as frequent sequelae. The purpose of this study was to develop a technique for measuring functional movement and examine the effect of brachial plexus injury location (preganglionic and postganglionic) on functional movement outcomes in a rat model of BPBI, which we achieved through integration of gait analysis with musculoskeletal modeling and simulation. Eight weeks following unilateral brachial plexus injury, sagittal plane shoulder and elbow angles were extracted from gait recordings of young rats (n = 18), after which rats were sacrificed for bilateral muscle architecture measurements. Musculoskeletal models reflecting animal-specific muscle architecture parameters were used to simulate gait and extract muscle fiber lengths. The preganglionic neurectomy group spent significantly less (p = 0.00116) time in stance and walked with significantly less (p < 0.05) elbow flexion and shoulder protraction in the affected limb than postganglionic neurectomy or control groups. Linear regression revealed no significant linear relationship between passive shoulder external rotation and functional shoulder protraction range of motion. Despite significant restriction in longitudinal muscle growth, normalized functional fiber excursions did not differ significantly between groups. In fact, when superimposed on a normalized force-length curve, neurectomy-impaired muscle fibers (except subscapularis) accessed regions of the curve that overlapped with the control group. Our results suggest the presence of compensatory motor control strategies during locomotion following BPBI. The clinical implications of our findings support emphasis on functional movement analysis in treatment of BPBI, as functional and passive outcomes may differ substantially.

Preganglionic and Postganglionic Brachial Plexus Birth Injury Effects on Shoulder Muscle Growth.

PURPOSE: Brachial plexus birth injury can differ in presentation, depending on whether the nerve ruptures distal to, or avulses proximal to, the dorsal root ganglion. More substantial contracture and bone deformity at the shoulder is typical in postganglionic injuries. However, changes to the underlying muscle structure that drive these differences in presentation are unclear. METHODS: Seventeen Sprague-Dawley rats received preganglionic or postganglionic neurectomy on a single limb on postnatal days 3 and 4. Muscles crossing the shoulder were retrieved once the rats were sacrificed at 8 weeks after birth. External rotation range of motion, muscle mass, muscle length, muscle sarcomere length, and calculated optimal muscle length were measured bilaterally. RESULTS: Average shoulder range of motion in the postganglionic group was 61.8% and 56.2% more restricted at 4 and 8 weeks, respectively, compared with that in the preganglionic group, but affected muscles after preganglionic injury were altered more severely (compared with the unaffected limb) than after postganglionic injury. Optimal muscle length in preganglionic injury was shorter in the affected limb (compared with the unaffected limb: -18.2% ± 9.2%) and to a greater extent than in postganglionic injury (-5.1% ± 6.2%). Muscle mass in preganglionic injury was lower in the affected limb (relative to the unaffected limb: -57.2% ± 24.1%) and to a greater extent than in postganglionic injury (-28.1% ± 17.7%). CONCLUSIONS: The findings suggest that the presence of contracture does not derive from restricted longitudinal muscle growth alone, but also depends on the extent of muscle mass loss occurring simultaneously after the injury. CLINICAL RELEVANCE: This study expands our understanding of differences in muscle architecture and the role of muscle structure in contracture formation for preganglionic and postganglionic brachial plexus birth injury.

Influence of Brachial Plexus Birth Injury Location on Glenohumeral Joint Morphology.

PURPOSE: Patient presentation after brachial plexus birth injury (BPBI) is influenced by nerve injury location; more contracture and bone deformity occur at the shoulder in postganglionic injuries. Although bone deformity after postganglionic injury is well-characterized, the extent of glenohumeral deformity after preganglionic BPBI is unclear. METHODS: Twenty Sprague-Dawley rat pups received preganglionic or postganglionic neurectomy on a single forelimb at postnatal days 3 to 4. Glenohumeral joints on affected and unaffected sides were analyzed using micro-computed tomography scans after death at 8 weeks after birth. Glenoid version, glenoid inclination, glenoid and humeral head radius of curvature, and humeral head thickness and width were measured bilaterally. RESULTS: The glenoid was significantly more declined in affected compared with unaffected shoulders after postganglionic (-17.7° ± 16.9°) but not preganglionic injury. Compared with the preganglionic group, the affected shoulder in the postganglionic group exhibited significantly greater declination and increased glenoid radius of curvature. In contrast, the humeral head was only affected after preganglionic but not postganglionic injury, with a significantly smaller humeral head radius of curvature (-0.2 ± 0.2 mm), thickness (-0.2 ± 0.3 mm), and width (-0.3 ± 0.4 mm) on the affected side compared with the unaffected side; changes in these metrics were significantly associated with each other. CONCLUSIONS: These findings suggest that glenoid deformities occur after postganglionic BPBI but not after preganglionic BPBI, whereas the humeral head is smaller after preganglionic injury, possibly suggesting an overall decreased biological growth rate in this group. CLINICAL RELEVANCE: This study expands understanding of the altered glenoid and humeral head morphologies after preganglionic BPBI and its comparisons with morphologies after postganglionic BPBI.

A minimally invasive technique for serial intraosseous perfusion measurements in the murine tibia using laser Doppler flowmetry.

In biomedical and preclinical research, the current standard method for measuring blood perfusion inside murine bone, radiolabeled microspheres, is a terminal procedure that cannot be used to monitor longitudinal perfusion changes. Laser Doppler flowmetry (LDF) can assess perfusion within the proximal tibial metaphysis of mice in vivo but requires a surgical procedure to place the measurement probe directly onto the bone surface. Sustained inflammation for over a month following this technique was previously reported, and previous studies have used LDF as an endpoint-only procedure. We developed a modified, minimally invasive LDF procedure to measure intraosseous perfusion in the murine tibia without stimulating local or systemic inflammation or inducing gait abnormalities. This modified technique can be used to measure perfusion weekly for up to at least a month in the murine tibia.•Unlike previous endpoint-only techniques, this modified LDF procedure can be performed weekly to monitor serial changes to intraosseous perfusion in the murine tibia•The modified LDF technique utilizes a smaller, more localized incision to minimize invasiveness and speed recovery.

Assessing changes in attitudes toward engineering and biomechanics resulting from a high school outreach event.

National Biomechanics Day aims to introduce students to the emerging field of biomechanics and improve their perception of engineering and engineers. This quantitative study examines participants' attitude changes following one such event. By prioritizing increasing excitement and engagement over teaching content, we anticipate that students' opinions of engineering and biomechanics will improve following the event. Pre- and post-test surveys consisting of Likert scale and semantic differential (SD) items assessed changes in three key areas: self-identity as a scientist and engineer, attitudes toward engineering, and attitudes toward biomechanics. Based on unpaired and paired student responses, we found significant gains in all three areas. Students agreed more strongly with statements regarding whether they saw themselves as scientists and engineers, and they had improved attitudes toward engineering in general and biomechanics specifically. The SD scales also reflected improved opinions of both science and biomechanics. These more positive attitudes could eventually lead to more students recruited to study a variety of engineering disciplines, ultimately addressing the ongoing national shortage of qualified engineers.

Integrated iterative musculoskeletal modeling predicts bone morphology following brachial plexus birth injury (BPBI).

Brachial plexus birth injury (BPBI) is the most common nerve injury among children. The glenohumeral joint of affected children can undergo severe osseous deformation and altered muscle properties, depending on location of the injury relative to the dorsal root ganglion (preganglionic or postganglionic). Preganglionic injury results in lower muscle mass and shorter optimal muscle length compared to postganglionic injury. We investigated whether these changes to muscle properties over time following BPBI provide a mechanically-driven explanation for observed differences in bone deformity between preganglionic and postganglionic BPBI. We developed a computational framework integrating musculoskeletal modeling to represent muscle changes over time and finite element modeling to simulate bone growth in response to mechanical and biological stimuli. The simulations predicted that the net glenohumeral joint loads in the postganglionic injury case were nearly 10.5% greater than in preganglionic. Predicted bone deformations were more severe in the postganglionic case, with the glenoid more declined (pre: -43.8°, post: -51.0°), flatter with higher radius of curvature (pre: 3.0 mm, post: 3.7 mm), and anteverted (pre: 2.53°, post: 4.93°) than in the preganglionic case. These simulated glenoid deformations were consistent with previous experimental studies. Thus, we concluded that the differences in muscle mass and length between the preganglionic and postganglionic injuries are critical mechanical drivers of the altered glenohumeral joint shape.

Influence of wire configuration on resistance to fragment distraction of tension bands placed in a greater trochanteric osteotomy model.

OBJECTIVE: To determine the influence of wiring configurations on initial tension and resistance to tensile loads in tension band constructs without the contributions of Kirschner-wire stabilization. STUDY DESIGN: Experimental study. SAMPLE POPULATION: A solid brass femur model manufactured on the basis of computed tomography of a normal right femur of a 30-kg dog modified by transection of the greater trochanter and placement of two pins that did not cross the simulated osteotomy. METHODS: Four tension band configurations were applied to the metal trochanteric osteotomy model: figure-of-eight with one twist (OT), figure-of-eight with two twists (TT), dual interlocking single loop, and double loop (DL). Configurations were tested under both monotonic loading (n = 8 per configuration) and incremental cyclic loading (n = 8 per configuration). Initial tension after tying, residual tension remaining after each cycle, and failure load at 2 mm of displacement (considered equivalent to clinical failure) were compared between configurations. RESULTS: The initial tension and the load to 2 mm of displacement were lower for OT wires compared with TT wires. The DL was the strongest and most stable configuration, generating 2.3 to 3.5 times greater initial tension, maintaining a greater percentage of residual tension under incremental cyclic loads, and resisting 2.0 to 2.4 times greater load before failure at 2 mm. Failure load was highly correlated with initial tension. CONCLUSION: Wire configurations reaching greater initial tension, such as the DL, allowed constructs to resist higher tensile loads. CLINICAL IMPACT: Wire configurations allowing higher initial tension may be warranted when tension bands are expected to sustain high tensile loads.

Minimally invasive laser Doppler flowmetry is suitable for serial bone perfusion measurements in mice.

In vivo laser Doppler flowmetry (LDF) has previously been used to quantify blood perfusion accurately at a single timepoint in the murine tibial metaphysis. However, this procedure entailed substantial disruption to soft tissues overlying the bone and caused notable localized inflammation for several weeks after the procedure, impeding serial measurements in the same mouse. In this study, we tested a less invasive technique to measure perfusion in the tibia with LDF and determined that it can be used serially in the same mouse without causing signs of inflammation or gait perturbations. Twenty 14-week-old C57Bl/6J mice were evenly divided into groups that either had daily treadmill exercise or remained sedentary. Within these activity groups, mice were evenly subdivided into groups that received LDF measurements either weekly or only once at the study endpoint. Bone perfusion was measured with LDF in the anteromedial region of the right tibial metaphysis. Serum concentrations of interleukin 6, incision site wound area, and interlimb coordination during gait were measured weekly for four weeks. Tibial perfusion did not differ significantly between exercise and sedentary groups within the weekly or endpoint-only LDF groups at any timepoint. Perfusion was significantly increased in the third week in the weekly LDF group relative to measurements in the second and fourth weeks. Ligation of the femoral artery caused consistent, rapid reductions in tibial perfusion, validating that LDF is sensitive to changes in tibial blood supply. Weekly LDF procedures did not adversely affect gait, as interlimb coordination during treadmill locomotion was similar between weekly and endpoint-only LDF groups at every timepoint. Images of the incision site show wound closure within one week, and serum concentrations of interleukin 6 were not significantly different between weekly and endpoint-only groups. Together, these findings demonstrate that our minimally invasive LDF technique is suitable for serial in vivo measurements of intraosseous blood perfusion without inducing localized inflammation or negatively affecting gait patterns in mice.

Stroke Prevents Exercise-Induced Gains in Bone Microstructure But Not Composition in Mice.

Ischemic stroke induces rapid loss in bone mineral density that is up to 13 times greater than during normal aging, leading to a markedly increased risk of fracture. Little is known about skeletal changes following stroke beyond density loss. In this study, we use a mild-moderate middle cerebral artery occlusion model to determine the effects of ischemic stroke without bedrest on bone microstructure, dynamic bone formation, and tissue composition. Twenty-seven 12-week-old male C57Bl/6J mice received either a stroke or sham surgery and then either received daily treadmill exercise or remained sedentary for 4 weeks. All mice were ambulatory immediately following stroke, and limb coordination during treadmill exercise was unaffected by stroke, indicating similar mechanical loading across limbs for both stroke and sham groups. Stroke did not directly detriment microstructure, but exercise only stimulated adaptation in the sham group, not the stroke group, with increased bone volume fraction and trabecular thickness in the sham distal femoral metaphysis. Stroke differentially decreased cortical area in the distal femoral metaphysis for the affected limb relative to the unaffected limb, as well as endosteal bone formation rate in the affected tibial diaphysis. Although exercise failed to improve bone microstructure following stroke, exercise increased mineral-to-matrix content in stroke but not sham. Together, these results show that stroke inhibits exercise-induced changes to femoral microstructure but not tibial composition, even without changes to gait. Similarly, affected-unaffected limb differences in cortical bone structure and bone formation rate in ambulatory mice show that stroke affects bone health even without bedrest.

Mass Spectrometry Imaging (MSI) of Fresh Bones using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI).

We report an effective strategy for direct analysis and two-dimensional (2D) matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) of mouse bones that underwent no chemical treatments prior to analysis. To unravel the chemistry in bones under near-physiological conditions, we cut a flash-frozen bone in half longitudinally, placed it in a mold facing flat side down, and poured Plaster of Paris on top of and around the bone. After Plaster of Paris had set, the bone with embedding material was removed from the mold, and placed on the IR-MALDESI imaging stage. Plaster of Paris acted as a fixture to keep every spot on the sample surface the same distance away from the laser focus. To demonstrate the feasibility of IR-MALDESI MSI for analyses of unmodified bones, we imaged bones derived from healthy and stroke-affected mice and generated ion heatmaps showing the spatial distribution of putatively annotated features.

Characterization of Tensioned PDMS Membranes for Imaging Cytometry on Microraft Arrays.

Polydimethylsiloxane (PDMS) membranes can act as sensing elements, barriers, and substrates, yet the low rigidity of the elastomeric membranes can limit their practical use in devices. Microraft arrays rely on a freestanding PDMS membrane as a substrate for cell arrays used in imaging cytometry and cellular isolation. However, the underlying PDMS membrane deforms under the weight of the cell media, making automated analytical microscopy (and thus cytometry and cell isolation) challenging. Here we report the development of microfabrication strategies and physically motivated mathematical modeling of membrane deformation of PDMS microarrays. Microraft arrays were fabricated with mechanical tension stored within the PDMS substrate. These membranes deformed 20× less than that of arrays fabricated using prior methods. Modeling of the deformation of pretensioned arrays using linear membrane theory yielded ≤15% error in predicting the array deflection and predicted the impact of cure temperatures up to 120 °C. A mathematical approach was developed to fit models of microraft shape to sparse real-world shape measurements. Automated imaging of cells on pretensioned microarrays using the focal planes predicted by the model produced high quality fluorescence images of cells, enabling accurate cell area quantification (<4% error) at increased speed (13×) relative to conventional methods. Our microfabrication method and simplified, linear modeling approach is readily applicable to control the deformation of similar membranes in MEMs devices, sensors, and microfluidics.

Thrombin-Responsive Transcutaneous Patch for Auto-Anticoagulant Regulation.

A thrombin-responsive closed-loop patch is developed for prolonged heparin delivery in a feedback-controlled manner. This microneedle-based patch can sense activated thrombin and subsequently releases heparin to prevent coagulation in the blood flow. This "smart" heparin patch can be transcutaneously inserted into skin without drug leakage and can sustainably regulate blood coagulation in response to thrombin.

Enhanced cellular infiltration of human adipose-derived stem cells in allograft menisci using a needle-punch method.

BACKGROUND: The meniscus plays a crucial role in knee joint stability, load transmission, and stress distribution. Meniscal tears are the most common reported knee injuries, and the current standard treatment for meniscal deficiency is meniscal allograft transplantation. A major limitation of this approach is that meniscal allografts do not have the capacity to remodel and maintain tissue homeostasis due to a lack of cellular infiltration. The purpose of this study was to provide a new method for enhanced cellular infiltration in meniscal allografts. METHODS: Twenty medial menisci were collected from cadaveric human sources and split into five experimental groups: (1) control native menisci, (2) decellularized menisci, (3) decellularized menisci seeded with human adipose-derived stem cells (hASC), (4) decellularized needle-punched menisci, and (5) decellularized needle-punched menisci seeded with hASC. All experimental allografts were decellularized using a combined method with trypsin EDTA and peracetic acid. Needle punching (1-mm spacing, 28 G microneedle) was utilized to improve porosity of the allograft. Samples were recellularized with hASC at a density of 250 k/g of tissue. After 28 days of in vitro culture, menisci were analyzed for mechanical, biochemical, and histological characteristics. RESULTS: Menisci maintained structural integrity and material properties (compressive equilibrium and dynamic moduli) throughout preparations. Increased DNA content was observed in the needle-punched menisci but not in the samples without needle punching. Histology confirmed these results, showing enhanced cellular infiltration in needle-punched samples. CONCLUSIONS: The enhanced infiltration achieved in this study could help meniscal allografts better remodel post-surgery. The integration of autologous adipose-derived stem cells could improve long-term efficacy of meniscal transplantation procedures by helping to maintain the meniscus in vivo.

Mechanical and Vascular Cues Synergistically Enhance Osteogenesis in Human Mesenchymal Stem Cells.

Development and maintenance of a vascular network are critical for bone growth and homeostasis; strategies that promote vascular function are critical for clinical success of tissue-engineered bone constructs. Co-culture of endothelial cells (ECs) with mesenchymal stem cells (MSCs) and exposure to 10% cyclic tensile strain have both been shown to regulate osteogenesis in isolation, but potential synergistic effects have yet to be explored. The objective of this study was to expose an MSC-EC co-culture to 10% cyclic tensile strain to examine the role of this mechanical stimulus on MSC-EC behavior. We hypothesized that paracrine signaling from ECs would stimulate osteogenesis of MSCs, and exposure to 10% cyclic tensile strain would enhance this anabolic signal. Human umbilical vein ECs and human bone marrow-derived MSCs were either monocultured or co-cultured at a 1:1 ratio in a mixed osteo/angiogenic medium, exposed to 10% cyclic tensile strain at 1 Hz for 4 h/day for 2 weeks, and biochemically and histologically analyzed for endothelial and osteogenic markers. While neither 10% cyclic tensile strain nor co-culture alone had a significant effect on osteogenesis, the concurrent application of strain to an MSC-EC co-culture resulted in a significant increase in calcium accretion and mineral deposition, suggesting that co-culture and strain synergistically enhance osteogenesis. Neither co-culture, 10% cyclic tensile strain, nor a combination of these stimuli affected endothelial markers, indicating that the endothelial phenotype remained stable, but unresponsive to the stimuli evaluated in this study. This study is the first to investigate the role of cyclic tensile strain on the complex interplay between ECs and MSCs in co-culture. The results of this study provide key insights into the synergistic effects of 10% cyclic tensile strain and co-culture on osteogenesis. Understanding mechanobiological factors affecting MSC-EC crosstalk will help enhance strategies for creating vascularized tissues in tissue engineering and regenerative medicine.

Reduced tissue-level stiffness and mineralization in osteoporotic cancellous bone.

Osteoporosis alters bone mass and composition ultimately increasing the fragility of primarily cancellous skeletal sites; however, effects of osteoporosis on tissue-level mechanical properties of cancellous bone are unknown. Dual-energy X-ray absorptiometry (DXA) scans are the clinical standard for diagnosing osteoporosis though changes in cancellous bone mass and mineralization are difficult to separate using this method. The goal of this study was to investigate possible difference in tissue-level properties with osteoporosis as defined by donor T scores. Spine segments from Caucasian female cadavers (58-92 years) were used. A T score for each donor was calculated from DXA scans to determine osteoporotic status. Tissue-level composition and mechanical properties of vertebrae adjacent to the scan region were measured using nanoindentation and Raman spectroscopy. Based on T scores, six samples were in the Osteoporotic group (58-74 years) and four samples were in the Not Osteoporotic group (65-92 years). The indentation modulus and mineral to matrix ratio (mineral:matrix) were lower in the Osteoporotic group than the Not Osteoporotic group. Mineral:matrix ratio decreased with age (r (2) = 0.35, p = 0.05), and the indentation modulus increased with areal bone mineral density (r (2) = 0.41, p = 0.04). This study is the first to examine cancellous bone composition and mechanical properties from a fracture prone location with osteoporosis. We found differences in tissue composition and mechanical properties with osteoporosis that could contribute to increased fragility in addition to changes in trabecular architecture and bone volume.

Tissue-engineered constructs of human oral mucosa examined by Raman spectroscopy.

A noninvasive quality monitoring of tissue-engineered constructs is a required component of any successful tissue-engineering technique. During a 2-week production period, ex vivo produced oral mucosa-equivalent constructs (EVPOMEs) may encounter adverse culturing conditions that might compromise their quality and render them ineffective. We demonstrate the application of near-infrared Raman spectroscopy to in vitro monitoring of EVPOMEs during their manufacturing process, with the ultimate goal of applying this technology in situ to monitor the grafted EVPOMEs. We identify Raman spectroscopic failure indicators for less-than optimal EVPOMEs that are stressed by higher temperature and exposure to higher than normal concentration of calcium ions. Raman spectra of EVPOMEs exposed to thermal and calcium stress showed correlation of the band height ratio of CH(2) deformation to phenylalanine ring breathing modes, providing a Raman metric to distinguish between viable and nonviable constructs. We compared these results to histology and glucose consumption measurements, demonstrating that Raman spectroscopy is more sensitive and specific to changes in proteins' secondary structure not visible by H&E histology. We also exposed the EVPOMEs to rapamycin, a cell growth inhibitor and cell proliferation capacity preserver, and distinguished between EVPOMEs pretreated with 2 nM rapamycin and controls, using the ratio of the Amide III envelope to the phenylalanine band as an indicator.

Whole bone mechanics and bone quality.

BACKGROUND: The skeleton plays a critical structural role in bearing functional loads, and failure to do so results in fracture. As we evaluate new therapeutics and consider treatments to prevent skeletal fractures, understanding the basic mechanics underlying whole bone testing and the key principles and characteristics contributing to the structural strength of a bone is critical. QUESTIONS/PURPOSES: We therefore asked: (1) How are whole bone mechanical tests performed and what are the key outcomes measured? (2) How do the intrinsic characteristics of bone tissue contribute to the mechanical properties of a whole bone? (3) What are the effects of extrinsic characteristics on whole bone mechanical behavior? (4) Do environmental factors affect whole bone mechanical properties? METHODS: We conducted a PubMed search using specific search terms and limiting our included articles to those related to in vitro testing of whole bones. Basic solid mechanics concepts are summarized in the context of whole bone testing and the determinants of whole bone behavior. RESULTS: Whole bone mechanical tests measure structural stiffness and strength from load-deformation data. Whole bone stiffness and strength are a function of total bone mass and the tissue geometric distribution and material properties. Age, sex, genetics, diet, and activity contribute to bone structural performance and affect the incidence of skeletal fractures. CONCLUSIONS: Understanding and preventing skeletal fractures is clinically important. Laboratory tests of whole bone strength are currently the only measures for in vivo fracture prediction. In the future, combined imaging and engineering models may be able to predict whole bone strength noninvasively.

Correcting fan-beam magnification in clinical densitometry scans of growing subjects.

As children grow, body and limb girths increase. For serial densitometric measurements, growth increases the distance between the bone region of interest and X-ray source over time, thereby increasing fan-beam magnification. To isolate bone accrual from magnification error in growing subjects, we developed a correction method based on waist girth, a common anthropometric measure. This correction was applied to dual-energy X-ray absorptiometry output obtained in a cohort of premenarcheal gymnasts and nongymnasts. After correcting for magnification, results for projected area and bone mineral content (BMC) increased by 0.4-1.1% at the lumbar spine and 8-16% at the femoral neck, decreasing areal bone mineral density (aBMD) by 0.4-2.3% at both sites. The effects of magnification correction were similar in magnitude to BMC and aBMD gains previously reported in longitudinal studies of normoactive children. Because of body size differences, the effect of correction for BMC and aBMD was 10-20% greater in nongymnasts than in gymnasts, which increased the observed aBMD differential between gymnasts and nongymnasts. Fan-beam magnification distorts true changes in bone mineral measures in growing premenarcheal girls and, therefore, may obscure additional activity-related changes during growth. Our correction technique may enhance detection of skeletal adaptation, particularly in pediatric populations.

Transcutaneous Raman spectroscopy of murine bone in vivo.

Raman spectroscopy can provide valuable information about bone tissue composition in studies of bone development, biomechanics, and health. In order to study the Raman spectra of bone in vivo, instrumentation that enhances the recovery of subsurface spectra must be developed and validated. Five fiber-optic probe configurations were considered for transcutaneous bone Raman spectroscopy of small animals. Measurements were obtained from the tibia of sacrificed mice, and the bone Raman signal was recovered for each probe configuration. The configuration with the optimal combination of bone signal intensity, signal variance, and power distribution was then evaluated under in vivo conditions. Multiple in vivo transcutaneous measurements were obtained from the left tibia of 32 anesthetized mice. After collecting the transcutaneous Raman signal, exposed bone measurements were collected and used as a validation reference. Multivariate analysis was used to recover bone spectra from transcutaneous measurements. To assess the validity of the transcutaneous bone measurements cross-correlations were calculated between standardized spectra from the recovered bone signal and the exposed bone measurements. Additionally, the carbonate-to-phosphate height ratios of the recovered bone signals were compared to the reference exposed bone measurements. The mean cross-correlation coefficient between the recovered and exposed measurements was 0.96, and the carbonate-to-phosphate ratios did not differ significantly between the two sets of spectra (p > 0.05). During these first systematic in vivo Raman measurements, we discovered that probe alignment and animal coat color influenced the results and thus should be considered in future probe and study designs. Nevertheless, our noninvasive Raman spectroscopic probe accurately assessed bone tissue composition through the skin in live mice.