@article{huang_cadet_king_cole_2022, title={Comparison of the mechanical properties and anchoring performance of polyvinylidene fluoride and polypropylene barbed sutures for tendon repair}, volume={6}, ISSN={["1552-4981"]}, url={https://doi.org/10.1002/jbm.b.35074}, DOI={10.1002/jbm.b.35074}, abstractNote={AbstractPolyvinylidene 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.}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Huang, Yihan and Cadet, Edwin R. and King, Martin W. and Cole, Jacqueline H.}, year={2022}, month={Jun} } @article{doering_britt_sawicki_cole_2021, title={Changes in Cellular Crosstalk between Skeletal Muscle Myoblasts and Bone Osteoblasts with Aging}, url={https://doi.org/10.1101/2021.04.26.441458}, DOI={10.1101/2021.04.26.441458}, abstractNote={AbstractMusculoskeletal function declines with aging, resulting in an increased incidence of trips and falls. Both bone and muscle experience age-related losses in tissue mass that alter their mechanical interactions in a well characterized manner, but changes in the biochemical interactions between bone and muscle with aging are not well understood. Of note, insulin-like growth factor 1 (IGF-1), a potent growth factor for bone and muscle, can be negatively altered with aging and may help explain losses in these tissues. We recently developed a co-culture system for simultaneous growth of bone mesenchymal stem cells (MSCs) and muscle satellite cells (SCs) to investigate the biochemical crosstalk between the two cell types. Here, we utilized an aging rat model to study cellular changes between young and old rat MSCs and SCs, in particular whether 1) young MSCs and SCs have increased proliferation and differentiation compared to old MSCs and SCs; 2) young cells have increased IGF-1 and collagen expression as a measure of crosstalk compared to old cells; and 3) young cells can mitigate the aging phenotype of old cells in co-culture. Rat MSCs and SCs were either mono- or co-cultured in Transwell® plates, grown to confluence, and allowed to differentiate for 14 days. Across the 14 days, cell proliferation was measured, with differentiation and crosstalk measurements evaluated at 14 days. The results suggest that in both young and old, proliferation is greater in mono-cultures compared to co-cultures, yet age and cell type did not have a significant effect. Differentiation did not differ between young and old cells, yet MSCs and SCs demonstrated the greatest amount of differentiation in co-culture. Finally, age, cell type, and culture type did not have a significant effect on collagen or IGF-1 expression. These results suggest co-culture may have a controlling effect, with the two cell types acting together to promote differentiation more than in mono-cultures, yet this response was not altered by age. In general, results for old cells had higher variability, suggesting a wider variety in the aging phenotypes demonstrated in these animals. This study was the first to use this rat aging model to investigate changes between bone and skeletal muscle cells, however further investigations are required to determine what signaling changes occur in response to age. Determining these signaling changes could lead to new targets for mitigating the progression of aging.}, author={Doering, Jonathan A. and Britt, Carly E. and Sawicki, Gregory S. and Cole, Jacqueline H.}, year={2021}, month={Apr} } @article{cox_smith_meulen_cole_2021, title={Heterogeneous Tissue Modulus Improved Prediction of Mechanical Behavior in Osteoporotic Vertebral Cancellous Bone}, url={https://doi.org/10.1101/2021.11.30.470675}, DOI={10.1101/2021.11.30.470675}, abstractNote={AbstractThe structural integrity of cancellous bone, which is essential to its skeletal load-bearing capacity, is governed chiefly by apparent density, trabecular architecture, and tissue material properties. Metabolic bone disorders such as osteoporosis can affect each of these factors, resulting in compromised load-bearing function and fracture. While the impact of apparent density and architecture on bone structural behavior is well-documented, much less is known about the influence of tissue material properties, particularly in osteoporotic bone. In this work, we isolated the influence of tissue modulus on normal and osteoporotic cancellous bone structural integrity, indicated by the apparent elastic modulus under uniaxial compression and patterns of internal tissue strain. Finite element (FE) models derived from 3D micro-computed tomography images were compared to physical testing data of the same samples. Three sets of FE models with increasing material detail were studied: 1) universal tissue elastic modulus (20 GPa), 2) specimen-specific average tissue modulus, and 3) heterogeneous tissue modulus. Applying a universal modulus resulted in overestimation of osteoporotic bone apparent modulus; applying specimen-specific material properties, either as a single average tissue modulus or heterogeneous distribution of tissue moduli, prevented significant apparent modulus overestimation. The greatest improvement in apparent modulus prediction resulted from incorporating a specimen-specific average tissue modulus, though using a specimen-specific heterogeneous tissue modulus provided the most reliable prediction of apparent modulus overall. In addition, median element strain in heterogeneous models also trended lower than in homogeneous models. This finding suggests that heterogeneous material properties may play a role in protective strain-concentrating mechanisms observed in cancellous bone. We conclude that future work exploring trabecular bone mechanics through finite element analysis should incorporate specimen-specific average tissue modulus at a minimum, but heterogeneous tissue modulus is recommended to maximize the functional similarity of boneinsilico with bonein vivo.}, author={Cox, Jason M. and Smith, Joshua D. and Meulen, Marjolein C. H. and Cole, Jacqueline H.}, year={2021}, month={Dec} } @article{doshi_reid_dixit_fawcett_cole_saul_2021, title={Location of brachial plexus birth injury affects functional outcomes in a rat model}, volume={9}, ISSN={["1554-527X"]}, url={https://doi.org/10.1002/jor.25173}, DOI={10.1002/jor.25173}, abstractNote={AbstractBrachial 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.}, journal={JOURNAL OF ORTHOPAEDIC RESEARCH}, publisher={Wiley}, author={Doshi, Raveena M. and Reid, Monique Y. and Dixit, Nikhil N. and Fawcett, Emily B. and Cole, Jacqueline H. and Saul, Katherine R.}, year={2021}, month={Sep} } @article{hanne_easter_stangeland-molo_cole_2020, title={A minimally invasive technique for serial intraosseous perfusion measurements in the murine tibia using laser Doppler flowmetry}, volume={7}, ISBN={2215-0161}, url={https://doi.org/10.1016/j.mex.2020.100814}, DOI={10.1016/j.mex.2020.100814}, abstractNote={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.}, journal={METHODSX}, publisher={Elsevier BV}, author={Hanne, Nicholas J. and Easter, Elizabeth D. and Stangeland-Molo, Sandra and Cole, Jacqueline H.}, year={2020}, pages={100814} } @article{teeter_husseini_cole_2020, title={Assessing changes in attitudes toward engineering and biomechanics resulting from a high school outreach event}, volume={103}, ISSN={0021-9290}, url={http://dx.doi.org/10.1016/j.jbiomech.2020.109683}, DOI={10.1016/j.jbiomech.2020.109683}, abstractNote={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.}, journal={Journal of Biomechanics}, publisher={Elsevier BV}, author={Teeter, Stephanie D. and Husseini, Naji S. and Cole, Jacqueline H.}, year={2020}, month={Apr}, pages={109683} } @article{cole_meulen_2020, title={Biomechanics of Bone}, ISBN={["978-3-319-69286-9"]}, ISSN={["2523-3793"]}, DOI={10.1007/978-3-319-69287-6_10}, journal={OSTEOPOROSIS: PATHOPHYSIOLOGY AND CLINICAL MANAGEMENT, 3RD EDITION}, author={Cole, Jacqueline H. and Meulen, Marjolein C. H.}, year={2020}, pages={185–209} } @article{fawcett_mccormick_murray_crouch_saul_cole_2020, title={Characterizing Trabecular Bone Properties near the Glenohumeral Joint Following Brachial Plexus Birth Injury}, url={https://doi.org/10.1101/2020.02.26.967224}, DOI={10.1101/2020.02.26.967224}, abstractNote={AbstractBrachial plexus birth injury (BPBI) causes functional arm impairment in 30-40% of those affected due to altered loading on the glenohumeral joint. While gross morphological osseous deformities have been seen in the humerus and scapula, alterations in the underlying trabecular bone microstructure and mineralization are not clear. Using a murine model of BPBI, trabecular bone alterations were explored in the proximal humerus and distal scapula, which surround the articulating surface of the joint. Samples were scanned using micro-CT, reoriented, and analyzed for standard trabecular metrics. The regions of interest closest to the articulating surface showed the greatest detriments. In the scapula, the scapular neck region showed less robust trabecular bone in the neurectomy group with decreased BV/TV (p=0.001), BMD (p=0.001), Conn.D (p=0.006), Tb.N (p<0.0001), and DA (p=0.033), and increased Tb.Sp (p<0.0001) compared to sham. In the humerus, the epiphysis showed less robust trabecular bone in neurectomy group, but to a much lesser extent than the scapular neck. The neurectomy group showed reduced BMD (p=0.007) and Tb.N (p=0.029) compared to sham. Data suggest deformities are worse near the articulating surface, likely due to the greater amount of mechanical loading. The reduction in trabecular microstructure and mineralization may compromise bone strength of the affected limb following BPBI. Further investigation of the underlying trabecular bone deformities following injury are necessary to eventually inform better treatments to limit the development of deformities.}, author={Fawcett, Emily B. and McCormick, Carolyn M. and Murray, Austin F. and Crouch, Dustin L. and Saul, Katherine R. and Cole, Jacqueline H.}, year={2020}, month={Feb} } @article{tushak_tamburro_fawcett_le_saul_cole_2020, title={Forelimb unloading impairs glenohumeral muscle development in growing rats}, url={https://doi.org/10.1101/2020.02.26.967273}, DOI={10.1101/2020.02.26.967273}, abstractNote={AbstractProper joint loading is essential for healthy musculoskeletal development. Many pediatric neuromuscular disorders cause irreversible muscle impairments resulting from both physiological changes and mechanical unloading of the joint. While previous studies have examined the effects of hindlimb unloading on musculoskeletal development in the lower limb, none have examined solely forelimb unloading. Thus, a large deficit in knowledge of the effect of upper limb unloading exists and must be addressed in order to better understand how the glenohumeral joint adapts during development. Two forelimb unloading models were developed to study the effects of varying degrees of unloading on the glenohumeral joint in growing rats: forelimb suspension (n=6, intervention 21 days post-natal) with complete unloading of both limbs via a novel suspension system and forearm amputation (n=8, intervention 3-6 days post-natal) with decreased loading and limb use in one limb after below-elbow amputation. After 8 weeks of unloading, changes in muscle architecture and composition were examined in ten muscles surrounding the shoulder. Results were compared to control rats from a previous study (n=8). Both methods of altered loading significantly affected muscle mass, sarcomere length, and optimal muscle length compared to control rats, with the biceps long head and triceps long head observing the most marked differences. Forearm amputation also significantly affected muscle mass, sarcomere length, and optimal muscle length in the affected limb relative to the contralateral limb. Muscle composition, assessed by collagen content, remained unchanged in all groups. This study demonstrated that forearm amputation, which was administered closer to birth, had greater effects on muscle than forelimb suspension, which was administered a few weeks later than amputation.}, author={Tushak, Sophia K. and Tamburro, Margaret K. and Fawcett, Emily B. and LE, Lauren E. Merritt and Saul, Katherine R. and Cole, Jacqueline H.}, year={2020}, month={Feb} } @article{dixit_mccormick_cole_saul_2021, title={Influence of Brachial Plexus Birth Injury Location on Glenohumeral Joint Morphology}, volume={46}, ISSN={["1531-6564"]}, DOI={10.1016/j.jhsa.2020.10.019}, abstractNote={{"Label"=>"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. {"Label"=>"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. {"Label"=>"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. {"Label"=>"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. {"Label"=>"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.}, number={6}, journal={JOURNAL OF HAND SURGERY-AMERICAN VOLUME}, author={Dixit, Nikhil N. and McCormick, Carolyn M. and Cole, Jacqueline H. and Saul, Katherine R.}, year={2021}, month={Jun} } @article{dixit_mcfarland_fisher_cole_saul_2020, title={Integrated iterative musculoskeletal modeling predicts bone morphology following brachial plexus birth injury (BPBI)}, volume={103}, url={https://doi.org/10.1016/j.jbiomech.2020.109658}, DOI={10.1016/j.jbiomech.2020.109658}, abstractNote={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.}, journal={Journal of Biomechanics}, publisher={Elsevier BV}, author={Dixit, Nikhil N. and McFarland, Daniel C. and Fisher, Matthew B. and Cole, Jacqueline H. and Saul, Katherine R.}, year={2020}, month={Apr}, pages={109658} } @article{dixit_mccormick_warren_cole_saul_2021, title={Preganglionic and Postganglionic Brachial Plexus Birth Injury Effects on Shoulder Muscle Growth}, volume={46}, ISSN={["1531-6564"]}, DOI={10.1016/j.jhsa.2020.07.017}, abstractNote={{"Label"=>"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. {"Label"=>"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. {"Label"=>"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%). {"Label"=>"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. {"Label"=>"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.}, number={2}, journal={JOURNAL OF HAND SURGERY-AMERICAN VOLUME}, author={Dixit, Nikhil N. and McCormick, Carolyn M. and Warren, Eric and Cole, Jacqueline H. and Saul, Katherine R.}, year={2021}, month={Feb} } @article{hanne_easter_stangeland-molo_cole_2019, title={A Minimally Invasive Technique for Serial Intraosseous Perfusion Measurements in the Murine Tibia Using Laser Doppler Flowmetry}, volume={7}, url={https://doi.org/10.1101/708453}, DOI={10.1101/708453}, abstractNote={AbstractIn 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 quantify 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. Unlike previous endpoint-only techniques, this modified LDF procedure can be performed weekly to monitor serial changes to intraosseous perfusion in the murine tibiaThe modified LDF technique utilizes a smaller, more localized incision to minimize invasiveness and speed recovery}, publisher={Cold Spring Harbor Laboratory}, author={Hanne, Nicholas J and Easter, Elizabeth D and Stangeland-Molo, Sandra and Cole, Jacqueline H}, year={2019}, month={Jul} } @article{hanne_steward_cox_easter_thornburg_sessions_pinnamaraju_cole_2019, title={High Fat Diet-Induced Obesity Negatively Affects Whole Bone Bending Strength but not Cortical Structure in the Femur}, volume={8}, url={https://doi.org/10.1101/729624}, DOI={10.1101/729624}, abstractNote={AbstractAlthough body mass index is positively associated with bone mineral density, suggesting obesity is protective against fracture, elderly obese individuals experience greater fracture risk at certain sites than non-obese peers, suggesting bone structural or material changes contribute to fragility. Diet-induced obesity rodent studies have reported detrimental changes to bone microstructure and some apparent-level material properties, but tissue-level material changes are not well understood. Because adipose tissue is highly vascularized, and bone remodeling depends critically on functional vascular supply, concurrent effects on osteovascular perfusion and structure may provide insight about obesity-related bone fragility. This study aimed to determine the effects of obesity on both tissue-level bone properties and osteovascular properties that could negatively impact bone strength. Five-week-old male C57Bl/6J mice were fed either high fat diet (HFD) or control fat diet (CFD) for 17 weeks and received daily treadmill exercise or remained sedentary for eight weeks at ages 14-22 weeks. HFD negatively affected femur bending strength, with 18% lower yield load than CFD. Although HFD negatively altered cancellous microstructure in the distal femur, with 32% lower bone volume fraction than CFD, it did not affect cortical bone geometry in the femoral metaphysis or diaphysis. HFD caused increased carbonate substitution but had no effect on other composition metrics or apparent- or tissue-level material properties in the femoral diaphysis. Exercise did not affect bone strength or microstructure but increased endosteal mineralizing surface in the tibial diaphysis, mineral crystallinity and mineral-to-matrix ratio in the femur, and blood supply to the proximal tibial metaphysis. HFD did not affect blood supply in the tibia or 2D osteovascular structure in the distal femoral metaphysis, indicating that HFD negatively affects cancellous bone without affecting osteovasculature. This study reveals that HFD negatively affected cancellous microstructure without affecting osteovascular structure, and whole-bone strength without altering cortical geometry or material properties.}, publisher={Cold Spring Harbor Laboratory}, author={Hanne, Nicholas J. and Steward, Andrew J. and Cox, Jason M. and Easter, Elizabeth D. and Thornburg, Hannah L. and Sessions, Marci R. and Pinnamaraju, Sriharsha V. and Cole, Jacqueline H.}, year={2019}, month={Aug} } @article{thompson_robe_roe_cole_2019, title={Influence of wire configuration on resistance to fragment distraction of tension bands placed in a greater trochanteric osteotomy model}, volume={49}, ISBN={1532-950X}, url={https://doi.org/10.1111/vsu.13350}, DOI={10.1111/vsu.13350}, abstractNote={AbstractObjectiveTo 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 designExperimental study.Sample populationA 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.MethodsFour 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.ResultsThe 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.ConclusionWire configurations reaching greater initial tension, such as the DL, allowed constructs to resist higher tensile loads.Clinical impactWire configurations allowing higher initial tension may be warranted when tension bands are expected to sustain high tensile loads.}, number={4}, journal={VETERINARY SURGERY}, publisher={Wiley}, author={Thompson, Elizabeth and Robe, Amir K. and Roe, Simon C. and Cole, Jacqueline H.}, year={2019}, pages={710–718} } @article{hanne_steward_geeroms_easter_thornburg_kerckhofs_parac-vogt_sheng_cole_2019, title={Ischemic Stroke Reduces Bone Perfusion and Alters Osteovascular Structure}, volume={8}, url={https://doi.org/10.1101/729632}, DOI={10.1101/729632}, abstractNote={AbstractRationaleStroke patients lose bone mass and experience fracture at an elevated rate. Although functional intraosseous vasculature is necessary for skeletal maintenance, the effect of stroke on osteovasculature is unknown.ObjectiveTo characterize changes to osteovascular function, structure, and composition following mild-to-moderate-severity ischemic stroke in mice, both with and without exercise therapy.Methods and ResultsTwelve-week-old male mice (n=27) received either a stroke (middle cerebral artery occlusion) or sham procedure, followed by four weeks of daily treadmill or sedentary activity. Intraosseous perfusion, measured weekly in the proximal tibial metaphysis, was reduced by stroke for two weeks. In the second week of recovery, exercise nearly restored perfusion to sham levels, and perfusion tended to be lower in the stroke-affected limb. At the conclusion of the study, osteovascular structure was assessed with contrast-enhanced computed tomography in the distal femoral metaphysis. Stroke significantly increased osteovascular volume and branching but reduced the relative number of blood vessels close to bone surfaces (6-22 µm away) and increased the relative number more than 52 µm away. These differences in vessel proximity to bone were driven by changes in the stroke-exercise group, indicating compounded effects of stroke and exercise. Exercise, but not stroke, nearly reduced the amount of osteogenic Type H blood vessels in the proximal tibial metaphysis, quantified with immunofluorescence microscopy.ConclusionsThis study is the first to examine the effects of stroke on osteovasculature. Stroke increased the amount of osteovasculature, but since blood vessels close to bone are associated with bone remodeling, the shift in osteovascular structure could play a role in bone loss following stroke. The exercise-induced reduction in the amount of Type H vessels and the stroke-exercise effect on osteovascular structure suggest moderate aerobic activity may have detrimental effects on bone remodeling during early stroke recovery.}, publisher={Cold Spring Harbor Laboratory}, author={Hanne, Nicholas J. and Steward, Andrew J. and Geeroms, Carla and Easter, Elizabeth D. and Thornburg, Hannah L. and Kerckhofs, Greet and Parac-Vogt, Tatjana and Sheng, Huaxin and Cole, Jacqueline H.}, year={2019}, month={Aug} } @article{khodjaniyazova_hanne_cole_muddiman_2019, title={Mass spectrometry imaging (MSI) of fresh bones using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI)}, volume={11}, ISSN={["1759-9679"]}, url={https://doi.org/10.1039/C9AY01886G}, DOI={10.1039/c9ay01886g}, abstractNote={Direct analysis and IR-MALDESI mass spectrometry imaging of fresh mouse bones that underwent no chemical treatments other than flash-freezing.}, number={46}, journal={ANALYTICAL METHODS}, publisher={Royal Society of Chemistry (RSC)}, author={Khodjaniyazova, Sitora and Hanne, Nicholas J. and Cole, Jacqueline H. and Muddiman, David C.}, year={2019}, month={Dec}, pages={5929–5938} } @article{hanne_easter_cole_2019, title={Minimally invasive laser Doppler flowmetry is suitable for serial bone perfusion measurements in mice}, volume={11}, url={https://doi.org/10.1016/j.bonr.2019.100231}, DOI={10.1016/j.bonr.2019.100231}, abstractNote={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.}, journal={Bone Reports}, publisher={Elsevier BV}, author={Hanne, Nicholas J. and Easter, Elizabeth D. and Cole, Jacqueline H.}, year={2019}, month={Dec}, pages={100231} } @article{hanne_steward_sessions_thornburg_sheng_cole_2019, title={Stroke Prevents Exercise-Induced Gains in Bone Microstructure But Not Composition in Mice}, volume={141}, ISSN={["1528-8951"]}, DOI={10.1115/1.4045113}, abstractNote={Abstract 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.}, number={12}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Hanne, Nicholas J. and Steward, Andrew J. and Sessions, Marci R. and Thornburg, Hannah L. and Sheng, Huaxin and Cole, Jacqueline H.}, year={2019}, month={Dec} } @article{hanne_steward_sessions_thornburg_sheng_cole_2019, title={Stroke prevents exercise-induced gains in bone microstructure but not composition in mice}, volume={7}, url={https://doi.org/10.1101/708388}, DOI={10.1101/708388}, abstractNote={ABSTRACTIschemic 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 four 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 affected limb relative to the unaffected limb of the distal femoral metaphysis, 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.}, publisher={Cold Spring Harbor Laboratory}, author={Hanne, Nicholas J. and Steward, Andrew J. and Sessions, Marci R. and Thornburg, Hannah L. and Sheng, Huaxin and Cole, Jacqueline H.}, year={2019}, month={Jul} } @article{hanne_easter_cole_2019, title={Validating Minimally Invasive Laser Doppler Flowmetry for Serial Bone Perfusion Measurements in Mice}, volume={7}, url={https://doi.org/10.1101/708412}, DOI={10.1101/708412}, abstractNote={AbstractIn 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 validated that it can be used serially in the same mouse without causing 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 can be used for serial in vivo measurements of intraosseous blood perfusion without inducing localized inflammation or negatively affecting gait patterns in mice.HighlightsModified, minimally invasive laser Doppler flowmetry (LDF) technique was validated for serial measures of tibial perfusion in mice.Weekly LDF procedures did not induce inflammation or alter gait patterns that could confound metrics of interest in bone studies.Ligation of the femoral artery confirmed the LDF technique measures functional perfusion within the bone.}, publisher={Cold Spring Harbor Laboratory}, author={Hanne, Nicholas J. and Easter, Elizabeth D. and Cole, Jacqueline H.}, year={2019}, month={Jul} } @article{disalvo_harris_kantesaria_pena_allbritton-king_cole_allbritton_2018, title={Characterization of Tensioned PDMS Membranes for Imaging Cytometry on Microraft Arrays}, volume={90}, ISSN={["1520-6882"]}, DOI={10.1021/acs.analchem.8b00176}, abstractNote={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.}, number={7}, journal={ANALYTICAL CHEMISTRY}, author={DiSalvo, Matthew and Harris, Daniel M. and Kantesaria, Saurin and Pena, Alexis N. and Allbritton-King, Jules D. and Cole, Jacqueline H. and Allbritton, Nancy L.}, year={2018}, month={Apr}, pages={4792–4800} } @article{thompson_robe_roe_cole_2018, title={Evaluating Wire Configurations for Tension Band Constructs using a Canine Greater Trochanteric Osteotomy Model}, volume={5}, url={https://doi.org/10.31224/osf.io/5yfsx}, DOI={10.31224/osf.io/5yfsx}, abstractNote={Objective: To investigate the stability of four tension band wiring configurations alone without the contributions of K-wire stabilization. Study design: ex vivo experimentalSample population: Sixty-four tension band wiring constructsMethods: Four tension band configurations were applied to a metal trochanteric osteotomy model based on a canine femur: figure-of-eight with one twist (OT), figure-of-eight with two twists (TT), dual interlocking single loop (DISL), and double loop (DL). Configurations were mechanically 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 recorded. Results: The initial tension and the load to 2 mm of displacement was lower for OT wires compared to TT wires. The DL was the strongest and most stable configuration, generating greater initial tension, maintaining a greater percentage of residual tension under incremental cyclic loads, and resisting higher load before failure at 2 mm. Failure load was highly correlated with initial tension. Conclusion: This model enabled evaluation of tension band wire configuration independent of the fixation pin portion of the construct. Wire configurations that can be tightened to a greater tension during tying, like the DL, are better able to resist the tensile loads experienced by the construct. Clinical impact: In clinical situations where high tensile loads are expected, a tighter, more secure tension band wire configuration may be warranted.}, publisher={Center for Open Science}, author={Thompson, Elizabeth and Robe, Amir K. and Roe, Simon C. and Cole, Jacqueline H.}, year={2018}, month={May} } @article{zhang_crawford_forbes_cole_king_2018, title={In Vitro Fatigue Evaluation of Chimney Endovascular Aneurysm Repair: A Case Study}, volume={68}, ISSN={["0741-5214"]}, DOI={10.1016/j.jvs.2018.06.186}, abstractNote={The objective was to evaluate the positional stability and physical properties of stent grafts and covered stents that have been used in an aortic arch chimney endovascular aneurysm repair (EVAR) for a specific patient who had a thoracoabdominal aneurysm. An accelerated mechanical fatigue test of 120 million cycles (3 life-years) was applied to a Cook stent graft and an Atrium covered stent that were deployed inside a customized polyurethane phantom using a chimney EVAR approach. They were then mounted on an ElectroForce (TA Instruments, New Castle, Del) accelerated fatigue tester. Fabrication of the polyurethane phantoms was based on the Digital Imaging and Communications in Medicine images of the patient. The fatigued phantom with the endovascular devices inside was monitored by computed tomography scans and endoscopy views to determine changes in the size and position of the devices. Postfatigue tests including scanning electron microscopy, bursting strength, and fabric count were performed to identify any changes in the physical properties of the stent graft fabric. The distal angle between the chimney covered stent and the thoracic stent graft experienced significant changes during 10 to 20 million cycles (129.53 ± 2.56 degrees and 127.13 ± 1.54 degrees, respectively) compared with the control group at zero cycles (134.97 ± 2.99 degrees; P < .05). The total length of the chimney covered stent changed significantly during the first 1 million cycles from 39.33 ± 0.05 mm to 38.03 ± 0.45 mm (P < .05). The proximal angle and area, bursting strength, and graft fabric count remained stable during fatiguing. No apparent surface abrasion was observed by scanning electron microscopy. This chimney EVAR approach for this particular patient maintained acceptable positional and dimensional stability based on this in vitro mechanical fatigue study that mimicked a 3-year life period. These conclusions are helpful in providing clinically relevant follow-up information for this particularly challenging patient who required the off-label use of two EVAR devices.}, number={3}, journal={JOURNAL OF VASCULAR SURGERY}, author={Zhang, Runqian and Crawford, Sean and Forbes, Thomas and Cole, Jacqueline H. and King, Martin W.}, year={2018}, month={Sep}, pages={E92–E92} } @phdthesis{cong_others_2018, title={Studies of Barbed Surgical Sutures Associated with Materials, Anchoring Performance and Histology.}, author={Cong, Hui and others}, year={2018} } @inproceedings{hanne_steward_easter_pinnamaraju_cole_2017, title={Diet-induced obesity deteriorates cancellous bone structure despite increased blood perfusion}, booktitle={Orthopaedic Research Society Annual Meeting, San Diego, CA, March 19-22}, author={Hanne, NJ and Steward, AJ and Easter, ED and Pinnamaraju, SV and Cole, JH}, year={2017} } @inproceedings{zhang_yu_wang_hanne_cui_qian_wang_xin_cole_gallippi_et al._2017, title={Smart Heparin Transcutaneous Patch}, booktitle={Society for Biomaterials Annual Meeting}, author={Zhang, Yuqi and Yu, Jicheng and Wang, Jinqiang and Hanne, Nicholas J and Cui, Zheng and Qian, Chenggen and Wang, Chao and Xin, Hongliang and Cole, Jacqueline H and Gallippi, Caterina M and et al.}, year={2017} } @article{zhang_yu_wang_hanne_cui_qian_wang_xin_cole_gallippi_et al._2017, title={Thrombin-responsive transcutaneous patch for auto-anticoagulant regulation}, volume={29}, DOI={10.1002/adma.201770028}, abstractNote={A thrombin-responsive microneedle-based transcutaneous patch is developed by C. M. Gallippi, Y. Zhu, Z. Gu, and co-workers, as demonstrated in article 1604043. The anticoagulant drug heparin is loaded into the hyaluronic acid needles through a thrombin cleavable peptide linker. This heparin patch can sense the thrombin level in blood vessels and autoregulate blood coagulation in a long-term manner. Cover design credit: Yuqi Zhang.}, number={4}, journal={Advanced Materials}, author={Zhang, Y. Q. and Yu, J. C. and Wang, J. Q. and Hanne, N. J. and Cui, Z. and Qian, C. G. and Wang, C. and Xin, H. L. and Cole, Jacqueline and Gallippi, C. M. and et al.}, year={2017} } @inproceedings{hanne_steward_easter_cole_2016, title={Bone blood perfusion increases with diet-induced obesity, associated with trabecular deterioration in mice}, booktitle={Biomedical Engineering Society Annual Meeting, Minneapolis, MN, October 5-8}, author={Hanne, NJ and Steward, AJ and Easter, ED and Cole, JH}, year={2016} } @inproceedings{thompson_roe_robe_cole_2016, title={Comparison of multiple tension band wire configurations on a greater trochanteric osteotomy model}, booktitle={American College of Veterinary Surgeons Surgery Summit, Seattle, WA, October 6-8}, author={Thompson, E and Roe, SC and Robe, AK and Cole, JH}, year={2016} } @article{nordberg_charoenpanich_vaughn_griffith_fisher_cole_spang_loboa_2016, title={Enhanced cellular infiltration of human adipose-derived stem cells in allograft menisci using a needle-punch method}, volume={11}, number={1}, journal={Journal of orthopaedic surgery and research}, publisher={BioMed Central}, author={Nordberg, Rachel C and Charoenpanich, Adisri and Vaughn, Christopher E and Griffith, Emily H and Fisher, Matthew B and Cole, Jacqueline H and Spang, Jeffrey T and Loboa, Elizabeth G}, year={2016}, pages={132} } @article{steward_cole_ligler_loboa_2016, title={Mechanical and Vascular Cues Synergistically Enhance Osteogenesis in Human Mesenchymal Stem Cells}, volume={22}, ISSN={["1937-335X"]}, DOI={10.1089/ten.TEA.2015.0533}, abstractNote={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.}, number={15-16}, journal={TISSUE ENGINEERING PART A}, author={Steward, Andrew J. and Cole, Jacqueline H. and Ligler, Frances S. and Loboa, Elizabeth G.}, year={2016}, month={Aug}, pages={997–1005} } @inproceedings{steward_cole_ligler_loboa_2016, title={The angiogenic and osteogenic effects of cyclic tensile strain on a co-culture of human MSCs and HUVECs}, booktitle={Orthopaedic Research Society Annual Meeting, Orlando, FL, March 5-8}, author={Steward, AJ and Cole, JH and Ligler, FS and Loboa, EG}, year={2016} } @article{zhang_yu_wang_hanne_cui_qian_wang_xin_cole_gallippi_et al._2017, title={Thrombin-Responsive Transcutaneous Patch for Auto-Anticoagulant Regulation}, volume={29}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201604043}, DOI={10.1002/ADMA.201604043}, abstractNote={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.}, number={4}, journal={Advanced Materials}, publisher={Wiley}, author={Zhang, Yuqi and Yu, Jicheng and Wang, Jinqiang and Hanne, Nicholas J. and Cui, Zheng and Qian, Chenggen and Wang, Chao and Xin, Hongliang and Cole, Jacqueline H. and Gallippi, Caterina M. and et al.}, year={2017}, month={Jan}, pages={1604043} } @article{kim_cole_boskey_baker_van der meulen_2014, title={Reduced Tissue-Level Stiffness and Mineralization in Osteoporotic Cancellous Bone}, volume={95}, ISSN={0171-967X 1432-0827}, url={http://dx.doi.org/10.1007/S00223-014-9873-4}, DOI={10.1007/S00223-014-9873-4}, abstractNote={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.}, number={2}, journal={Calcified Tissue International}, publisher={Springer Science and Business Media LLC}, author={Kim, Grace and Cole, Jacqueline H. and Boskey, Adele L. and Baker, Shefford P. and van der Meulen, Marjolein C. H.}, year={2014}, month={Jun}, pages={125–131} } @article{kim_cole_boskey_baker_meulen_2014, title={Reduced tissue-level stiffness and mineralization in osteoporotic cancellous bone}, volume={95}, number={2}, journal={Calcified tissue international}, publisher={Springer US}, author={Kim, Grace and Cole, Jacqueline H and Boskey, Adele L and Baker, Shefford P and Meulen, Marjolein CH}, year={2014}, pages={125–131} } @article{cole_graf_patel_koch_britton_alford_zernicke_kozloff_2013, title={Oxygen-Dependent Mineralization Differences with High Intrinsic Aerobic Capacity are Associated with Osteoblast Extracellular Matrix Gene Expression}, volume={28}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000332035803130&KeyUID=WOS:000332035803130}, number={Suppl 1}, journal={Journal of Bone and Mineral Research}, publisher={WILEY-BLACKWELL}, author={Cole, Jacqueline and Graf, Kristin and Patel, Parth and Koch, Lauren and Britton, Steven and Alford, Andrea and Zernicke, Ronald and Kozloff, Kenneth}, year={2013}, pages={SA0218} } @inproceedings{cole_koch_britton_zernicke_kozloff_2012, title={Hypoxia disrupts osteoblast proliferation and mineralization in rats with high intrinsic aerobic capacity}, volume={27}, number={Suppl 1}, booktitle={JOURNAL OF BONE AND MINERAL RESEARCH}, author={Cole, Jacqueline and Koch, Lauren and Britton, Steven and Zernicke, Ronald and Kozloff, Kenneth}, year={2012}, pages={MO0230} } @article{khmaladze_ganguly_raghavan_kuo_cole_marcelo_feinberg_izumi_morris_mahadevanjansen_et al._2012, title={Raman Spectroscopic Analysis of Human Tissue Engineered Oral Mucosa Constructs (EVPOME) Perturbed by Physical and Biochemical Methods}, volume={8219}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000302563700012&KeyUID=WOS:000302563700012}, DOI={10.1117/12.908281}, abstractNote={We show the application of near-infrared Raman Spectroscopy to in-vitro monitoring of the viability of tissue constructs (EVPOMEs). During their two week production period EVPOME may encounter thermal, chemical or biochemical stresses that could cause development to cease, rendering the affected constructs useless. We discuss the development of a Raman spectroscopic technique to study EVPOMEs noninvasively, with the ultimate goal of applying it in-vivo. We identify Raman spectroscopic failure indicators for EVPOMEs, which are stressed by temperature, and discuss the implications of varying calcium concentration and pre-treatment of the human keratinocytes with Rapamycin. In particular, Raman spectra show correlation of the peak height ratios of CH2 deformation to phenylalanine ring breathing, providing a Raman metric to distinguish between viable and nonviable constructs. We also show the results of singular value decomposition analysis, demonstrating the applicability of Raman spectroscopic technique to both distinguish between stressed and non-stressed EVPOME constructs, as well as between EVPOMEs and bare AlloDerm® substrates, on which the oral keratinocytes have been cultured. We also discuss complications arising from non-uniform thickness of the AlloDerm® substrate and the cultured constructs, as well as sampling protocols used to detect local stress and other problems that may be encountered in the constructs.}, journal={Biomedical Vibrational Spectroscopy V: Advances in Research and Industry}, author={Khmaladze, Alexander and Ganguly, Arindam and Raghavan, Mekhala and Kuo, Shiuhyang and Cole, Jacqueline H. and Marcelo, Cynthia L. and Feinberg, Stephen E. and Izumi, Kenji and Morris, Michael D. and MahadevanJansen, A and et al.}, year={2012} } @inproceedings{khmaladze_ganguly_raghavan_kuo_cole_marcelo_feinberg_izumi_morris_2012, title={Raman spectroscopic analysis of human tissue engineered oral mucosa constructs (EVPOME) perturbed by physical and biochemical methods}, volume={8219}, booktitle={Biomedical Vibrational Spectroscopy V: Advances in Research and Industry}, author={Khmaladze, Alexander and Ganguly, Arindam and Raghavan, Mekhala and Kuo, Shiuhyang and Cole, Jacqueline H and Marcelo, Cynthia L and Feinberg, Stephen E and Izumi, Kenji and Morris, Michael D}, year={2012}, pages={82190J} } @inproceedings{cole_tramer_white_koch_britton_zernicke_kozloff_2012, title={Rats with high intrinsic aerobic capacity retain increased femoral cortical thickness with aging}, booktitle={Orthopaedic Research Society Annual Meeting, San Francisco, CA}, author={Cole, JH and Tramer, JS and White, LE and Koch, LG and Britton, SL and Zernicke, RF and Kozloff, KM}, year={2012} } @article{khmaladze_ganguly_kuo_raghavan_kainkaryam_cole_izumi_marcelo_feinberg_morris_2013, title={Tissue-Engineered Constructs of Human Oral Mucosa Examined by Raman Spectroscopy}, volume={19}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000315214500006&KeyUID=WOS:000315214500006}, DOI={10.1089/ten.tec.2012.0287}, abstractNote={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.}, number={4}, journal={Tissue Engineering Part C-Methods}, author={Khmaladze, Alexander and Ganguly, Arindam and Kuo, Shiuhyang and Raghavan, Mekhala and Kainkaryam, Raghu and Cole, Jacqueline H. and Izumi, Kenji and Marcelo, Cynthia L. and Feinberg, Stephen E. and Morris, Michael D.}, year={2013}, pages={299–306} } @article{khmaladze_ganguly_kuo_raghavan_kainkaryam_cole_izumi_marcelo_feinberg_morris_2012, title={Tissue-engineered constructs of human oral mucosa examined by Raman spectroscopy}, volume={19}, number={4}, journal={Tissue Engineering Part C: Methods}, publisher={Mary Ann Liebert, Inc. 140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA}, author={Khmaladze, Alexander and Ganguly, Arindam and Kuo, Shiuhyang and Raghavan, Mekhala and Kainkaryam, Raghu and Cole, Jacqueline H and Izumi, Kenji and Marcelo, Cynthia L and Feinberg, Stephen E and Morris, Michael D}, year={2012}, pages={299–306} } @inproceedings{cole_tayim_welker_halonen_goulet_koch_britton_zernicke_alford_kozloff_2011, title={Intrinsic aerobic capacity influences osteoblast proliferation, differentiation, and mineralization in vitro}, booktitle={Orthopaedic Research Society Annual Meeting, Long Beach, CA}, author={Cole, JH and Tayim, RJ and Welker, EM and Halonen, NR and Goulet, GC and Koch, LG and Britton, SL and Zernicke, RF and Alford, AI and Kozloff, KM}, year={2011} } @article{cole_van der meulen_2011, title={Whole Bone Mechanics and Bone Quality}, volume={469}, ISSN={0009-921X 1528-1132}, url={http://dx.doi.org/10.1007/S11999-011-1784-3}, DOI={10.1007/S11999-011-1784-3}, abstractNote={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.}, number={8}, journal={Clinical Orthopaedics and Related Research®}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Cole, Jacqueline H. and van der Meulen, Marjolein C. H.}, year={2011}, month={Jan}, pages={2139–2149} } @article{cole_meulen_2011, title={Whole bone mechanics and bone quality}, volume={469}, number={8}, journal={Clinical Orthopaedics and Related Research®}, publisher={Springer-Verlag}, author={Cole, Jacqueline H and Meulen, Marjolein CH}, year={2011}, pages={2139–2149} } @inbook{cole_meulen_2010, title={Biomechanics of bone}, booktitle={Osteoporosis}, publisher={Humana Press}, author={Cole, Jacqueline H and Meulen, Marjolein CH}, year={2010}, pages={157–179} } @inproceedings{tayim_cole_halonen_goulet_koch_britton_zernicke_alford_kozloff_2010, title={Differences in oxygen consumption rate of osteoblast lineage cells in rats bred for high and low aerobic capacity}, volume={25}, number={Suppl 1}, booktitle={JOURNAL OF BONE AND MINERAL RESEARCH}, author={Tayim, Riyad and Cole, Jacqueline and Halonen, Neil and Goulet, Grant and Koch, Lauren and Britton, Steven and Zernicke, Ronald and Alford, Andrea and Kozloff, Kenneth}, year={2010}, pages={SA0241} } @article{goulet_halonen_cole_koch_britton_morris_zernicke_kozloff_2010, title={Influence of Intrinsic Aerobic Exercise Capacity on Skeletal Health}, volume={42}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000290226302793&KeyUID=WOS:000290226302793}, number={5}, journal={Medicine and Science in Sports and Exercise}, publisher={Medicine & Science in Sports & Exercise}, author={Goulet, Grant C. and Halonen, Neil R. and Cole, Jaqueline H. and Koch, Lauren G. and Britton, Steve L. and Morris, Michael D. and Zernicke, Ronald F. and Kozloff, Ken M.}, year={2010}, pages={821} } @inproceedings{influence of intrinsic and trained aerobic capacity on bone mineralization and material properties_2010, booktitle={Orthopaedic Research Society Annual Meeting, New Orleans, LA}, year={2010} } @inproceedings{halonen_tayim_goulet_cole_clifford_goldstein_koch_britton_zernicke_alford_et al._2010, title={Intrinsic aerobic capacity influences MSC proliferation, mineralization, and fracture healing}, booktitle={Orthopaedic Research Society Annual Meeting, New Orleans, LA}, author={Halonen, NR and Tayim, R and Goulet, GC and Cole, JH and Clifford, C and Goldstein, SA and Koch, LG and Britton, SL and Zernicke, RF and Alford, AI and et al.}, year={2010} } @inproceedings{pre-clinical feasibility study of a novel implant for treatment of a cartilage defect in the medial femoral condyle_2010, booktitle={Orthopaedic Research Society Annual Meeting, New Orleans, LA}, year={2010} } @article{cole_meulen_adler_2010, title={Biomechanics of Bone}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000273414500007&KeyUID=WOS:000273414500007}, DOI={10.1007/978-1-59745-459-9_7}, abstractNote={The ability to bear loads is a critical function of the skeleton, in addition to its metabolic and physiological roles. Load-bearing ability depends on both the applied loads and the structural properties of the loaded bone. When the loads exceed the structural properties, fracture will occur. Because the nature of the applied loads can be difficult to predict, the greatest potential impact on minimizing fracture risk is through targeted interventions and therapies to improve bone strength. The strength and fracture resistance of the skeleton depend primarily on the mass, morphology/architecture, and material properties of bone tissue. Although each of these attributes has been examined independently in both cortical and cancellous bone, no single measurement can fully characterize the structural integrity of bone or reliably predict the occurrence of a fracture. In addition, factors such as aging, trauma, and disease affect the tissue properties and can compromise bone strength. While bone mass and, more recently, morphology have been widely examined in vivo, to date these measures do not fully explain variations in bone mechanical properties observed experimentally in vitro. Healthy bone tissue exhibits spatial and temporal variations in tissue-level material properties that are altered by aging and disease. Characterizing bone material properties, whether at the tissue level or at the chemical composition level of the mineral and matrix constituents, may improve the ability to predict structural competence and fracture risk reliably.}, journal={Osteoporosis: Pathophysiology and Clinical Management, Second Edition}, author={Cole, Jacqueline H. and Meulen, Marjolein C. H. and Adler, RA}, year={2010}, pages={157–179} } @article{cole_dowthwaite_scerpella_van der meulen_2009, title={Correcting Fan-Beam Magnification in Clinical Densitometry Scans of Growing Subjects}, volume={12}, ISSN={1094-6950}, url={http://dx.doi.org/10.1016/j.jocd.2009.05.002}, DOI={10.1016/j.jocd.2009.05.002}, abstractNote={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.}, number={3}, journal={Journal of Clinical Densitometry}, publisher={Elsevier BV}, author={Cole, Jacqueline H. and Dowthwaite, Jodi N. and Scerpella, Tamara A. and van der Meulen, Marjolein C.H.}, year={2009}, month={Jul}, pages={322–329} } @article{cole_dowthwaite_scerpella_meulen_2009, title={Correcting fan-beam magnification in clinical densitometry scans of growing subjects}, volume={12}, number={3}, journal={Journal of Clinical Densitometry}, publisher={Elsevier}, author={Cole, Jacqueline H and Dowthwaite, Jodi N and Scerpella, Tamara A and Meulen, Marjolein CH}, year={2009}, pages={322–329} } @inproceedings{cole_halonen_yoon_koch_britton_goldstein_zernicke_morris_kozloff_2009, title={Differential effects of intrinsic aerobic capacity and exercise training on bone composition and structure}, volume={24}, number={Suppl 1}, booktitle={JOURNAL OF BONE AND MINERAL RESEARCH}, author={Cole, Jacqueline and Halonen, Neil and Yoon, Lisa and Koch, Lauren and Britton, Steven and Goldstein, Steven and Zernicke, Ronald and Morris, Michael and Kozloff, Kenneth}, year={2009}, pages={SA0024} } @inproceedings{kim_cole_baker_boskey_meulen_2009, title={Relating material properties and composition in osteoporotic bone tissue}, booktitle={Orthopaedic Research Society Annual Meeting, Las Vegas, NV}, author={Kim, Grace and Cole, Jacqueline and Baker, Shefford and Boskey, Adele and Meulen, Marjolein}, year={2009} } @article{schulmerich_cole_kreider_esmonde-white_dooley_goldstein_morris_2009, title={Transcutaneous Raman Spectroscopy of Murine Bone In Vivo}, volume={63}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000264142600004&KeyUID=WOS:000264142600004}, number={3}, journal={Applied Spectroscopy}, publisher={SAGE Publications Sage UK: London, England}, author={Schulmerich, Matthew V. and Cole, Jacqueline H. and Kreider, Jaclynn M. and Esmonde-White, Francis and Dooley, Kathryn A. and Goldstein, Steven A. and Morris, Michael D.}, year={2009}, pages={286–295} } @inproceedings{cole_halonen_yoon_koch_britton_goldstein_zernicke_morris_kozloff_2009, title={Variation in bone tissue structure and composition with rats selectively bred for high and low aerobic running capacity}, booktitle={39th Annual IBMS Sun Valley Workshop on Musculoskeletal Biology, Sun Valley, ID}, author={Cole, Jacqueline H and Halonen, Neil R and Yoon, Lisa S and Koch, Lauren G and Britton, Steven L and Goldstein, Steven A and Zernicke, Ronald F and Morris, Michael D and Kozloff, Kenneth M}, year={2009} } @article{srinivasan_schulmerich_cole_dooley_kreider_pogue_morris_goldstein_2008, title={Image-guided Raman spectroscopic recovery of canine cortical bone contrast in situ}, volume={16}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000258368600059&KeyUID=WOS:000258368600059}, DOI={10.1364/OE.16.012190}, abstractNote={Raman scattering provides valuable biochemical and molecular markers for studying bone tissue composition with use in predicting fracture risk in osteoporosis. Raman tomography can image through a few centimeters of tissue but is limited by low spatial resolution. X-ray computed tomography (CT) imaging can provide high-resolution image-guidance of the Raman spectroscopic characterization, which enhances the quantitative recovery of the Raman signals, and this technique provides additional information to standard imaging methods. This hypothesis was tested in data measured from Teflon tissue phantoms and from a canine limb. Image-guided Raman spectroscopy (IG-RS) of the canine limb using CT images of the tissue to guide the recovery recovered a contrast of 145:1 between the cortical bone and background. Considerably less contrast was found without the CT image to guide recovery. This study presents the first known IG-RS results from tissue and indicates that intrinsically high contrasts (on the order of a hundred fold) are available.}, number={16}, journal={Optics Express}, publisher={Optical Society of America}, author={Srinivasan, Subhadra and Schulmerich, Matthew and Cole, Jacqueline H. and Dooley, Kathryn A. and Kreider, Jaclynn M. and Pogue, Brian W. and Morris, Michael D. and Goldstein, Steven A.}, year={2008}, pages={12190–12200} } @inproceedings{microdamage assessment in rat cortical bone by light scattering_2008, booktitle={Orthopaedic Research Society Annual Meeting, San Francisco, CA}, year={2008} } @article{cole_waldorff_schulmerich_dooley_goldstein_morris_2008, title={Non-invasive Detection of Bone Microdamage by Light Scattering.}, volume={23}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000259411002596&KeyUID=WOS:000259411002596}, journal={Journal of Bone and Mineral Research}, author={Cole, J. H. and Waldorff, E. I. and Schulmerich, M. V. and Dooley, K. A. and Goldstein, S. A. and Morris, M. D.}, year={2008}, pages={S492} } @inproceedings{non-invasive detection of bone microdamage by light scattering._2008, volume={23}, booktitle={JOURNAL OF BONE AND MINERAL RESEARCH}, year={2008}, pages={S492–S492} } @article{dooley_schulmerich_kreider_cole_goldstein_morris_2008, title={Non-invasive In Vivo Raman Spectroscopy in Mice.}, volume={23}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000259411002114&KeyUID=WOS:000259411002114}, journal={Journal of Bone and Mineral Research}, author={Dooley, K. A. and Schulmerich, M. V. and Kreider, J. M. and Cole, J. H. and Goldstein, S. A. and Morris, M. D.}, year={2008}, pages={S366} } @inproceedings{non-invasive in vivo raman spectroscopy in mice._2008, volume={23}, booktitle={JOURNAL OF BONE AND MINERAL RESEARCH}, year={2008}, pages={S366–S366} } @inproceedings{cole_waldorff_schulmerich_dooley_goldstein_morris_2008, title={Non-invasive detection of bone microdamage by light scattering}, volume={23}, number={Suppl 1}, booktitle={JOURNAL OF BONE AND MINERAL RESEARCH}, author={Cole, Jacqueline and Waldorff, Erik and Schulmerich, Matthew and Dooley, Kathryn and Goldstein, Steven and Morris, Michael}, year={2008}, pages={S492} } @article{schulmerich_cole_dooley_morris_kreider_goldstein_srinivasan_pogue_2008, title={Noninvasive Raman tomographic imaging of canine bone tissue}, volume={13}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000256438300003&KeyUID=WOS:000256438300003}, DOI={10.1117/1.2904940}, abstractNote={Raman spectroscopic diffuse tomographic imaging has been demonstrated for the first time. It provides a noninvasive, label-free modality to image the chemical composition of human and animal tissue and other turbid media. This technique has been applied to image the composition of bone tissue within an intact section of a canine limb. Spatially distributed 785-nm laser excitation was employed to prevent thermal damage to the tissue. Diffuse emission tomography reconstruction was used, and the location that was recovered has been confirmed by micro-computed tomography (micro-CT) images.}, number={2}, journal={Journal of Biomedical Optics}, publisher={International Society for Optics and Photonics}, author={Schulmerich, Matthew V. and Cole, Jacqueline H. and Dooley, Kathryn A. and Morris, Michael D. and Kreider, Jaclynn M. and Goldstein, Steven A. and Srinivasan, Subhadra and Pogue, Brian W.}, year={2008}, pages={020506} } @article{schulmerich_cole_dooley_morris_kreider_goldstein_2008, title={Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue}, volume={13}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000256438300012&KeyUID=WOS:000256438300012}, DOI={10.1117/1.2892687}, abstractNote={The effect of optical clearing with glycerol on the Raman spectra of bone tissue acquired transcutaneously on right and left tibiae from four mice is studied. Multiple transcutaneous measurements are obtained from each limb; glycerol is then applied as an optical clearing agent, and additional transcutaneous measurements are taken. Glycerol reduces the noise in the raw spectra (p=0.0037) and significantly improves the cross-correlation between the recovered bone factor and the exposed bone measurement in a low signal-to-noise region of the bone spectra (p=0.0245).}, number={2}, journal={Journal of Biomedical Optics}, publisher={International Society for Optics and Photonics}, author={Schulmerich, Matthew V. and Cole, Jacqueline H. and Dooley, Kathryn A. and Morris, Michael D. and Kreider, Jaclynn M. and Goldstein, Steven A.}, year={2008}, pages={021108} } @inproceedings{schulmerich_srinivasan_kreider_cole_dooley_goldstein_pogue_morris_2008, title={Raman tomography of tissue phantoms and bone tissue}, volume={6853}, booktitle={Biomedical Optical Spectroscopy}, author={Schulmerich, Matthew V and Srinivasan, Subhadra and Kreider, Jaclynn and Cole, Jacqueline H and Dooley, Kathryn A and Goldstein, Steven A and Pogue, Brian W and Morris, Michael D}, year={2008}, pages={68530V} } @inbook{schulmerich_srinivasan_kreider_cole_dooley_goldstein_pogue_morris_mahadevanjansen_petrich_et al._2008, title={Raman tomography of tissue phantoms and bone tissue - art. no. 68530V}, volume={6853}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000255591800019&KeyUID=WOS:000255591800019}, DOI={10.1117/12.763837}, abstractNote={We report tomographic reconstruction of objects located several millimeters below the surface of highly scattering media. For this purpose we adapted proven software developed for fluorescence tomography with and without the use of spatial priors1. For this first demonstration we acquired Raman spectra using an existing ring/disk fiber optic probe with fifty collection fibers2. Several illumination ring diameters were employed to generate multiple angles of incidence. Tomographic reconstruction from Raman scatter was tested using a 9.5 mm diameter Teflon® sphere embedded in a gel of agarose and 1% Intralipid. Blind reconstruction of the sphere using the 732 cm-1 C-F stretch yielded an accurate shape but an inaccurate depth. Using the known shape and position of the object as spatial priors, a more accurate reconstruction was obtained. We also demonstrated a reconstruction of the tibial diaphysis of an intact canine hind limb using spatial priors generated from micro-computed tomography. In this first demonstration of Raman tomography in animal tissue, the P-O stretch of the bone mineral at 958 cm-1 was used for the reconstruction. An accurate shape and depth were recovered.}, booktitle={Biomedical Optical Spectroscopy}, author={Schulmerich, Matthew. V. and Srinivasan, Subhadra. and Kreider, Jaclynn. and Cole, Jacqueline. H. and Dooley, Kathryn A. and Goldstein, Steven. A. and Pogue, Brian. W. and Morris, Michael. D. and MahadevanJansen, A and Petrich, W and et al.}, year={2008}, pages={V8530} } @inproceedings{cole_schulmerich_dooley_izumi_kreider_daley_feinberg_goldstein_morris_2007, title={Characterization of bone and soft tissue composition by Raman spectroscopy}, volume={189}, booktitle={Cells Tissues Organs}, author={Cole, Jacqueline and Schulmerich, Matthew and Dooley, Kathryn and Izumi, Kenji and Kreider, Jaclynn and Daley, Ethan and Feinberg, Stephen and Goldstein, Steven and Morris, Michael}, year={2007}, pages={300} } @article{cole_myers_meulen_2007, title={Finite element models more accurately predict structural behavior of human cancellous bone when using specimen-specific tissue properties}, volume={22}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000250509101201&KeyUID=WOS:000250509101201}, journal={Journal of Bone and Mineral Research}, author={Cole, J. H. and Myers, E. R. and Meulen, M. C. H.}, year={2007}, pages={S225} } @inproceedings{cole_myers_meulen_2007, title={Finite element models more accurately predict structural behavior of human cancellous bone when using specimen-specific tissue properties}, volume={22}, booktitle={JOURNAL OF BONE AND MINERAL RESEARCH}, author={Cole, JH and Myers, ER and Meulen, MCH}, year={2007}, pages={S225–S225} } @article{cole_schulmerich_dooley_kriegl_daley_goldstein_morris_2007, title={Measurement protocols for the non-invasive assessment of bone constituent properties by Raman Spectroscopy}, volume={22}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000250509101329&KeyUID=WOS:000250509101329}, journal={Journal of Bone and Mineral Research}, author={Cole, J. H. and Schulmerich, M. V. and Dooley, K. A. and Kriegl, J. M. and Daley, E. and Goldstein, S. A. and Morris, M. D.}, year={2007}, pages={S257} } @inproceedings{measurement protocols for the non-invasive assessment of bone constituent properties by raman spectroscopy_2007, volume={22}, booktitle={Journal of Bone and Mineral Research}, year={2007}, pages={S257–S257} } @article{cole_2007, title={The role of architecture and tissue properties in the structural integrity of human vertebral cancellous bone}, author={Cole, Jacqueline Heather}, year={2007} } @article{cole_myers_meulen_2006, title={MicroCT and DXA mineral measures fail to predict material properties in the human lumbar spine.}, volume={21}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000240866303036&KeyUID=WOS:000240866303036}, journal={Journal of Bone and Mineral Research}, author={Cole, J. H. and Myers, E. R. and Meulen, M. C. H.}, year={2006}, pages={S352} } @inproceedings{cole_myers_meulen_2006, title={MicroCT and DXA mineral measures fail to predict material properties in the human lumbar spine.}, volume={21}, booktitle={JOURNAL OF BONE AND MINERAL RESEARCH}, author={Cole, JH and Myers, ER and Meulen, MCH}, year={2006}, pages={S352–S352} } @article{cole_scerpella_meulen_2005, title={Fan-beam densitometry of the growing skeleton}, volume={8}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000227538200009&KeyUID=WOS:000227538200009}, DOI={10.1385/JCD:8:1:057}, abstractNote={Magnification error in fan-beam densitometers varies with distance from the X-ray source to the bone measured and might obscure bone mineral changes in the growing skeleton. Magnification was examined by scanning aluminum rods of different shapes (square, rectangular, solid round, and hollow round) at four distances above the X-ray source in two orientations, with rods aligned parallel (SI) and perpendicular (ML) to the longitudinal axis of the scanning table. Measured area (cm(2)) decreased linearly with distance above the X-ray source for all rods in the SI orientation (p < 0.005). Measured mineral content (g) decreased linearly with distance but only for SI round rods (p < 0.0001) and for ML hollow round rods (p < 0.005). Area and mineral content decreased 1.6-1.8% per centimeter above the source for round rods. Measured mineral density (g/cm(2)) decreased linearly with distance from the source only for ML hollow round rods (p < 0.005). Variation in area, mineral content, and mineral density measurements was 6.6-6.9%, 6.9-7.5%, and 1.9-2.3%, respectively, for SI round rods. Magnification errors of this magnitude are problematic for clinical studies using fan-beam densitometry. Particularly in pediatric subjects, increases in soft tissue during normal growth could increase a bone's distance from the fan-beam source and result in apparent reductions in area and bone mineral content.}, number={1}, journal={Journal of Clinical Densitometry}, author={Cole, JH and Scerpella, TA and Meulen, MCH}, year={2005}, pages={57–64} } @article{cole_scerpella_meulen_2005, title={Fan-beam densitometry of the growing skeleton: are we measuring what we think we are?}, volume={8}, number={1}, journal={Journal of Clinical Densitometry}, publisher={Elsevier}, author={Cole, Jacqueline H and Scerpella, Tamara A and Meulen, Marjolein CH}, year={2005}, pages={57–64} } @article{gero_cole_kanaley_meulen_scerpella_2005, title={Increased bone accrual in premenarcheal gymnasts: A longitudinal study}, volume={17}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000229381100005&KeyUID=WOS:000229381100005}, number={2}, journal={Pediatric Exercise Science}, author={Gero, N and Cole, J and Kanaley, J and Meulen, M and Scerpella, T}, year={2005}, pages={149–160} } @article{cole_kent_bhudhikanok_bachrach_meulen_2004, title={Normal bone geometry but reduced bone mineral at the femoral neck with cystic fibrosis.}, volume={19}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000224326801303&KeyUID=WOS:000224326801303}, journal={Journal of Bone and Mineral Research}, author={Cole, JH and Kent, K and Bhudhikanok, GS and Bachrach, LK and Meulen, MC}, year={2004}, pages={S237} } @inproceedings{cole_kent_bhudhikanok_bachrach_meulen_2004, title={Normal bone geometry but reduced bone mineral at the femoral neck with cystic fibrosis.}, volume={19}, booktitle={JOURNAL OF BONE AND MINERAL RESEARCH}, author={Cole, JH and Kent, K and Bhudhikanok, GS and Bachrach, LK and Meulen, MC}, year={2004}, pages={S237–S237} } @inproceedings{cole_scerpella_meulen_2004, title={Use of a phantom to assess fan-beam magnification in clinical densitometry}, booktitle={Orthopaedic Research Society Annual Meeting, San Francisco, CA}, author={Cole, JH and Scerpella, TA and Meulen, MCH}, year={2004} } @inproceedings{cole_gero_meulen_scerpella_2003, title={Modest amounts of impact activity increase the rate of bone mineral accrual in pre-menarcheal gymnasts: a longitudinal study}, booktitle={Orthopaedic Research Society Annual Meeting, New Orleans, LA}, author={Cole, JH and Gero, NM and Meulen, MCH and Scerpella, TA}, year={2003} } @article{cole_kent_bhudhikanok_bachrach_meulen_2003, title={Patients with cystic fibrosis have normal bone geometry but reduced bone mineral.}, volume={18}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000186080501284&KeyUID=WOS:000186080501284}, journal={Journal of Bone and Mineral Research}, author={Cole, JH and Kent, K and Bhudhikanok, GS and Bachrach, LK and Meulen, MCH}, year={2003}, pages={S320} } @inproceedings{cole_kent_bhudhikanok_bachrach_meulen_2003, title={Patients with cystic fibrosis have normal bone geometry but reduced bone mineral.}, volume={18}, booktitle={JOURNAL OF BONE AND MINERAL RESEARCH}, author={Cole, JH and Kent, K and Bhudhikanok, GS and Bachrach, LK and Meulen, MCH}, year={2003}, pages={S320–S320} }