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  1. Article: Harnessing mechanical cues in the cellular microenvironment for bone regeneration.

    Josephson, Timothy O / Morgan, Elise F

    Frontiers in physiology

    2023  Volume 14, Page(s) 1232698

    Abstract: At the macroscale, bones experience a variety of compressive and tensile loads, and these loads cause deformations of the cortical and trabecular microstructure. These deformations produce a variety of stimuli in the cellular microenvironment that can ... ...

    Abstract At the macroscale, bones experience a variety of compressive and tensile loads, and these loads cause deformations of the cortical and trabecular microstructure. These deformations produce a variety of stimuli in the cellular microenvironment that can influence the differentiation of marrow stromal cells (MSCs) and the activity of cells of the MSC lineage, including osteoblasts, osteocytes, and chondrocytes. Mechanotransduction, or conversion of mechanical stimuli to biochemical and biological signals, is thus part of a multiscale mechanobiological process that drives bone modeling, remodeling, fracture healing, and implant osseointegration. Despite strong evidence of the influence of a variety of mechanical cues, and multiple paradigms proposed to explain the influence of these cues on tissue growth and differentiation, even a working understanding of how skeletal cells respond to the complex combinations of stimuli in their microenvironments remains elusive. This review covers the current understanding of what types of microenvironmental mechanical cues MSCs respond to and what is known about how they respond in the presence of multiple such cues. We argue that in order to realize the vast potential for harnessing the cellular microenvironment for the enhancement of bone regeneration, additional investigations of how combinations of mechanical cues influence bone regeneration are needed.
    Language English
    Publishing date 2023-10-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2023.1232698
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  2. Article ; Online: A Review of CT-Based Fracture Risk Assessment with Finite Element Modeling and Machine Learning.

    Fleps, Ingmar / Morgan, Elise F

    Current osteoporosis reports

    2022  Volume 20, Issue 5, Page(s) 309–319

    Abstract: Purpose of review: We reviewed advances over the past 3 years in assessment of fracture risk based on CT scans, considering methods that use finite element models, machine learning, or a combination of both.: Recent findings: Several studies have ... ...

    Abstract Purpose of review: We reviewed advances over the past 3 years in assessment of fracture risk based on CT scans, considering methods that use finite element models, machine learning, or a combination of both.
    Recent findings: Several studies have demonstrated that CT-based assessment of fracture risk, using finite element modeling or biomarkers derived from machine learning, is equivalent to currently used clinical tools. Phantomless calibration of CT scans for bone mineral density enables accurate measurements from routinely taken scans. This opportunistic use of CT scans for fracture risk assessment is facilitated by high-quality automated segmentation with deep learning, enabling workflows that do not require user intervention. Modeling of more realistic and diverse loading conditions, as well as improved modeling of fracture mechanisms, has shown promise to enhance our understanding of fracture processes and improve the assessment of fracture risk beyond the performance of current clinical tools. CT-based screening for fracture risk is effective and, by analyzing scans that were taken for other indications, could be used to expand the pool of people screened, therefore improving fracture prevention. Finite element modeling and machine learning both provide valuable tools for fracture risk assessment. Future approaches should focus on including more loading-related aspects of fracture risk.
    MeSH term(s) Bone Density ; Finite Element Analysis ; Fractures, Bone/diagnostic imaging ; Humans ; Machine Learning ; Risk Assessment/methods ; Tomography, X-Ray Computed
    Language English
    Publishing date 2022-09-01
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2186581-4
    ISSN 1544-2241 ; 1544-1873
    ISSN (online) 1544-2241
    ISSN 1544-1873
    DOI 10.1007/s11914-022-00743-w
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6146: Show issues Location:
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  3. Article ; Online: Geometric determinants of the mechanical behavior of image-based finite element models of the intervertebral disc.

    Fleps, Ingmar / Newman, Harrah R / Elliott, Dawn M / Morgan, Elise F

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society

    2024  Volume 42, Issue 6, Page(s) 1343–1355

    Abstract: The intervertebral disc is an important structure for load transfer through the spine. Its injury and degeneration have been linked to pain and spinal fractures. Disc injury and spine fractures are associated with high stresses; however, these stresses ... ...

    Abstract The intervertebral disc is an important structure for load transfer through the spine. Its injury and degeneration have been linked to pain and spinal fractures. Disc injury and spine fractures are associated with high stresses; however, these stresses cannot be measured, necessitating the use of finite element (FE) models. These models should include the disc's complex structure, as changes in disc geometry have been linked to altered mechanical behavior. However, image-based models using disc-specific structures have yet to be established. This study describes a multiphasic FE modeling approach for noninvasive estimates of subject-specific intervertebral disc mechanical behavior based on medical imaging. The models (n = 22) were used to study the influence of disc geometry on the predicted global mechanical response (moments and forces), internal local disc stresses, and tractions at the interface between the disc and the bone. Disc geometry was found to have a strong influence on the predicted moments and forces on the disc (R
    MeSH term(s) Finite Element Analysis ; Intervertebral Disc/diagnostic imaging ; Intervertebral Disc/physiology ; Humans ; Biomechanical Phenomena ; Adult ; Male ; Female ; Stress, Mechanical ; Middle Aged ; Lumbar Vertebrae/diagnostic imaging ; Lumbar Vertebrae/physiology ; Models, Biological
    Language English
    Publishing date 2024-01-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 605542-4
    ISSN 1554-527X ; 0736-0266
    ISSN (online) 1554-527X
    ISSN 0736-0266
    DOI 10.1002/jor.25788
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1879: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Multiscale theoretical model shows that aging-related mechanical degradation of cortical bone is driven by microstructural changes in addition to porosity.

    Marty, André Gutiérrez / Barbone, Paul E / Morgan, Elise F

    Journal of the mechanical behavior of biomedical materials

    2023  Volume 145, Page(s) 106029

    Abstract: This study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To that end, cortical bone was modeled as a bundle of elastic-plastic, parallel fibers, ...

    Abstract This study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To that end, cortical bone was modeled as a bundle of elastic-plastic, parallel fibers, which represented osteons and interstitial tissue, loaded in uniaxial tension. Distinct material properties were assigned to each fiber in either the osteon or interstitial fiber "families." Models representative of mature (20-60 yrs.) bone, and elderly (60+) bone were created by modeling aging via the following changes to the input parameters: (i) increasing porosity from 5% to 15%, (ii) increasing the ratio of the number of osteon fibers relative to interstitial fibers from 40% to 50%, and (iii) changing the fiber material properties from representing mature bone samples to representing elderly bone samples (i.e., increased strength and decreased toughness of interstitial fibers together with decreased toughness of osteon fibers). To understand the respective contributions of these changes, additional models isolating one or two of each of these were also created. From the computed stress-strain curve for the fiber bundle, the yield point (ϵ
    MeSH term(s) Humans ; Aged ; Porosity ; Bone and Bones ; Cortical Bone/physiology ; Aging/physiology ; Models, Theoretical ; Haversian System
    Language English
    Publishing date 2023-07-18
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2378381-3
    ISSN 1878-0180 ; 1751-6161
    ISSN (online) 1878-0180
    ISSN 1751-6161
    DOI 10.1016/j.jmbbm.2023.106029
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  5. Article ; Online: Effect of fabric on the accuracy of computed tomography-based finite element analyses of the vertebra.

    Wu, Yuanqiao / Morgan, Elise F

    Biomechanics and modeling in mechanobiology

    2019  Volume 19, Issue 2, Page(s) 505–517

    Abstract: Quantitative computed tomography (QCT)-based finite element (FE) models of the vertebra are widely used in studying spine biomechanics and mechanobiology, but their accuracy has not been fully established. Although the models typically assign material ... ...

    Abstract Quantitative computed tomography (QCT)-based finite element (FE) models of the vertebra are widely used in studying spine biomechanics and mechanobiology, but their accuracy has not been fully established. Although the models typically assign material properties based only on local bone mineral density (BMD), the mechanical behavior of trabecular bone also depends on fabric. The goal of this study was to determine the effect of incorporating measurements of fabric on the accuracy of FE predictions of vertebral deformation. Accuracy was assessed by using displacement fields measured via digital volume correlation-applied to time-lapse microcomputed tomography (μCT)-as the gold standard. Two QCT-based FE models were generated from human L1 vertebrae (n = 11): the entire vertebral body and a cuboid-shaped portion of the trabecular centrum [dimensions: (20-30) × (15-20) × (15-20) mm
    MeSH term(s) Biomechanical Phenomena ; Bone Density ; Computer Simulation ; Elastic Modulus ; Female ; Finite Element Analysis ; Humans ; Male ; Models, Biological ; Spine/diagnostic imaging ; Tomography, X-Ray Computed
    Language English
    Publishing date 2019-09-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2093052-5
    ISSN 1617-7940 ; 1617-7959
    ISSN (online) 1617-7940
    ISSN 1617-7959
    DOI 10.1007/s10237-019-01225-2
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5966: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  6. Article ; Online: Generation of Closed Transverse Fractures in Small Animals.

    De Giacomo, Anthony / Morgan, Elise F / Gerstenfeld, Louis C

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2230, Page(s) 63–73

    Abstract: The most common procedure that has been developed for use in rats and mice to model fracture healing is described. The nature of the regenerative processes that may be assessed and the types of research questions that may be addressed with this model are ...

    Abstract The most common procedure that has been developed for use in rats and mice to model fracture healing is described. The nature of the regenerative processes that may be assessed and the types of research questions that may be addressed with this model are briefly outlined. The detailed surgical protocol to generate closed simple transverse fractures is presented and general considerations when setting up an experiment using this model are described.
    MeSH term(s) Animals ; Biomechanical Phenomena ; Disease Models, Animal ; Fracture Healing/physiology ; Fractures, Closed/physiopathology ; Fractures, Closed/surgery ; Humans ; Male ; Mice ; Rats
    Language English
    Publishing date 2020-10-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1028-2_4
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  7. Article ; Online: Overview of Skeletal Repair (Fracture Healing and Its Assessment).

    Morgan, Elise F / Giacomo, Anthony De / Gerstenfeld, Louis C

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2230, Page(s) 17–37

    Abstract: The study of postnatal skeletal repair is of immense clinical interest. Optimal repair of skeletal tissue is necessary in all varieties of elective and reparative orthopedic surgical treatments. However, the repair of fractures is unique in this context ... ...

    Abstract The study of postnatal skeletal repair is of immense clinical interest. Optimal repair of skeletal tissue is necessary in all varieties of elective and reparative orthopedic surgical treatments. However, the repair of fractures is unique in this context in that fractures are one of the most common traumas that humans experience and are the end-point manifestation of osteoporosis, the most common chronic disease of aging. In the first part of this introduction the basic biology of fracture healing is presented. The second part discusses the primary methodological approaches that are used to examine repair of skeletal hard tissue and specific considerations for choosing among and implementing these approaches.
    MeSH term(s) Aging/pathology ; Fracture Healing ; Fractures, Bone/physiopathology ; Fractures, Bone/therapy ; Humans ; Musculoskeletal System/physiopathology ; Osteoporosis/physiopathology ; Osteoporosis/therapy
    Language English
    Publishing date 2020-11-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1028-2_2
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  8. Article ; Online: Biomechanical structure-function relations for human trabecular bone - comparison of calcaneus, femoral neck, greater trochanter, proximal tibia, and vertebra.

    Sadoughi, Saghi / Bevill, Grant / Morgan, Elise F / Palepu, Vivek / Keaveny, Tony M / Wear, Keith A

    Computer methods in biomechanics and biomedical engineering

    2022  Volume 26, Issue 5, Page(s) 508–516

    Abstract: MicroCT-based finite element models were used to compute power law relations for uniaxial compressive yield stress versus bone volume fraction for 78 cores of human trabecular bone from five anatomic sites. The leading coefficient of the power law for ... ...

    Abstract MicroCT-based finite element models were used to compute power law relations for uniaxial compressive yield stress versus bone volume fraction for 78 cores of human trabecular bone from five anatomic sites. The leading coefficient of the power law for calcaneus differed from those for most of the other sites (
    MeSH term(s) Humans ; Femur Neck/diagnostic imaging ; Tibia/diagnostic imaging ; Cancellous Bone/diagnostic imaging ; Calcaneus/diagnostic imaging ; Femur/diagnostic imaging ; Spine ; Hip Fractures ; Bone Density
    Language English
    Publishing date 2022-05-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2071764-7
    ISSN 1476-8259 ; 1025-5842
    ISSN (online) 1476-8259
    ISSN 1025-5842
    DOI 10.1080/10255842.2022.2069465
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6374: Show issues Location:
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  9. Article: An

    Kendall, Jack J / Ledoux, Charles / Marques, Francisco C / Boaretti, Daniele / Schulte, Friederike A / Morgan, Elise F / Müller, Ralph

    Frontiers in bioengineering and biotechnology

    2023  Volume 11, Page(s) 1289127

    Abstract: Bone defects represent a challenging clinical problem as they can lead to non-union. ...

    Abstract Bone defects represent a challenging clinical problem as they can lead to non-union.
    Language English
    Publishing date 2023-12-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2023.1289127
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  10. Article: Spatial assessment of femoral neck bone density and microstructure in hip osteoarthritis.

    Auger, Joshua D / Naik, Amartya J / Murakami, Akira M / Gerstenfeld, Louis C / Morgan, Elise F

    Bone reports

    2021  Volume 16, Page(s) 101155

    Abstract: Osteoarthritis (OA) is known to involve profound changes in bone density and microstructure near to, and even distal to, the joint. Critically, however, a full, spatial picture of these abnormalities has not been well documented in a quantitative fashion ...

    Abstract Osteoarthritis (OA) is known to involve profound changes in bone density and microstructure near to, and even distal to, the joint. Critically, however, a full, spatial picture of these abnormalities has not been well documented in a quantitative fashion in hip OA. Here, micro-computed tomography (44.8 μm/voxel) and data-driven computational anatomy were used to generate 3-D maps of the distribution of bone density and microstructure in human femoral neck samples with early (6F/4M, mean age = 51.3 years), moderate (14F/8M, mean age = 60 years), and severe (16F/6M, mean age = 63.3 years) radiographic OA. With increasing severity of radiographic OA, there was decreased cortical bone mineral density (BMD) (
    Language English
    Publishing date 2021-12-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2821774-3
    ISSN 2352-1872
    ISSN 2352-1872
    DOI 10.1016/j.bonr.2021.101155
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