scholarly journals The association between mineralised tissue formation and the mechanical local in vivo environment: Time-lapsed quantification of a mouse defect healing model

2019 ◽  
Author(s):  
Duncan C Tourolle né Betts ◽  
Esther Wehrle ◽  
Graeme R Paul ◽  
Gisela A Kuhn ◽  
Patrik Christen ◽  
...  
Keyword(s):  
Healing Process ◽  
Strong Association ◽  
Mechanical Strain ◽  
Mechanical Stimuli ◽  
Tissue Formation ◽  
Micro Computed Tomography ◽  
Element Analysis ◽  
Cross Sectional ◽  
Mechanical Signal

AbstractAn improved understanding of how local mechanical stimuli guide the fracture healing process has the potential to enhance clinical treatment of bone injury. Recent preclinical studies of bone defect in animal models have used cross-sectional data to examine this phenomenon indirectly. In this study, a direct time-lapsed imaging approach was used to investigate the local mechanical strains that precede the formation of mineralised tissue at the tissue scale. The goal was to test two hypotheses: 1) the local mechanical signal that precedes the onset of tissue mineralisation is higher in areas which mineralise, and 2) this local mechanical signal is independent of the magnitude of global mechanical loading of the tissue in the defect. Two groups of mice with femoral defects of length 0.85 mm (n=10) and 1.45 mm (n=9) were studied, allowing for distinct distributions of tissue scale strains in the defects. The regeneration and (re)modelling of mineralised tissue was observed weekly using in vivo micro-computed tomography (micro-CT), which served as a ground truth for resolving areas of mineralised tissue formation. The mechanical environment was determined using micro-finite element analysis (micro-FE) on baseline images. The formation of mineralised tissue showed strong association with areas of higher mechanical strain (area-under-the-curve: 0.91±0.04, true positive rate: 0.85±0.05) while surface based strains could correctly classify 43% of remodelling events. These findings support our hypotheses by showing a direct association between the local mechanical strains and the formation of mineralised tissue.

scholarly journals Progressive recruitment of distal MEC-4 channels determines touch response strength in C. elegans

2019 ◽  
Author(s):  
S. Katta ◽  
A. Sanzeni ◽  
A. Das ◽  
M. Vergassola ◽  
M.B. Goodman
Keyword(s):  
Temporal Dynamics ◽  
Mechanical Strain ◽  
Tissue Mechanics ◽  
Mechanical Stimuli ◽  
Patch Clamp Recording ◽  
Open Probability ◽  
C Elegans ◽  
Somatosensory Neurons ◽  
Touch Response

AbstractTouch deforms, or strains, the skin beyond the immediate point of contact. The spatiotemporal nature of the touch-induced strain fields depend on the mechanical properties of the skin and the tissues below. Somatosensory neurons that sense touch branch out within the skin and rely on a set of mechano-electrical transduction channels distributed within their dendrites to detect mechanical stimuli. Here, we sought to understand how tissue mechanics shape touch-induced mechanical strain across the skin over time and how individual channels located in different regions of the strain field contribute to the overall touch response. We leveraged C. elegans’ touch receptor neurons (TRNs) as a simple model amenable to in vivo whole-cell patch clamp recording and an integrated experimental-computational approach to dissect the mechanisms underlying the spatial and temporal dynamics that we observed. Consistent with the idea that strain is produced at a distance, we show that delivering strong stimuli outside the anatomical extent of the neuron is sufficient to evoke MRCs. The amplitude and kinetics of the MRCs depended on both stimulus displacement and speed. Finally, we found that the main factor responsible for touch sensitivity is the recruitment of progressively more distant channels by stronger stimuli, rather than modulation of channel open probability. This principle may generalize to somatosensory neurons with more complex morphologies.SummaryThrough experiment and simulation, Katta et al. reveal that pushing faster and deeper recruits more and more distant mechano-electrical transduction channels during touch. The net result is a dynamic receptive field whose size and shape depends on tissue mechanics, stimulus parameters, and channel distribution within sensory neurons.

scholarly journals Progressive recruitment of distal MEC-4 channels determines touch response strength in C. elegans

2019 ◽  
Vol 151 (10) ◽  
pp. 1213-1230 ◽  
Author(s):  
Samata Katta ◽  
Alessandro Sanzeni ◽  
Alakananda Das ◽  
Massimo Vergassola ◽  
Miriam B. Goodman
Keyword(s):  
Temporal Dynamics ◽  
Mechanical Strain ◽  
Response Strength ◽  
Tissue Mechanics ◽  
Mechanical Stimuli ◽  
Patch Clamp Recording ◽  
Open Probability ◽  
Somatosensory Neurons ◽  
Touch Response

Touch deforms, or strains, the skin beyond the immediate point of contact. The spatiotemporal nature of the touch-induced strain fields depend on the mechanical properties of the skin and the tissues below. Somatosensory neurons that sense touch branch out within the skin and rely on a set of mechano-electrical transduction channels distributed within their dendrites to detect mechanical stimuli. Here, we sought to understand how tissue mechanics shape touch-induced mechanical strain across the skin over time and how individual channels located in different regions of the strain field contribute to the overall touch response. We leveraged Caenorhabditis elegans’ touch receptor neurons as a simple model amenable to in vivo whole-cell patch-clamp recording and an integrated experimental-computational approach to dissect the mechanisms underlying the spatial and temporal dynamics we observed. Consistent with the idea that strain is produced at a distance, we show that delivering strong stimuli outside the anatomical extent of the neuron is sufficient to evoke MRCs. The amplitude and kinetics of the MRCs depended on both stimulus displacement and speed. Finally, we found that the main factor responsible for touch sensitivity is the recruitment of progressively more distant channels by stronger stimuli, rather than modulation of channel open probability. This principle may generalize to somatosensory neurons with more complex morphologies.

A 3d Histomorphometric Method for Analyses of Skeletal Tissue Mechanobiology

2007 ◽  
Author(s):  
Ryan E. Gleason ◽  
Kristy T. S. Palomares ◽  
Thomas A. Einhorn ◽  
Louis C. Gerstenfeld ◽  
Elise F. Morgan
Keyword(s):  
Healing Process ◽  
Fracture Site ◽  
Cartilage Tissue ◽  
In Vivo Model ◽  
Original Form ◽  
Mechanical Stimuli ◽  
Fracture Callus ◽  
Skeletal Tissue ◽  
Form And Function

Skeletal repair and regeneration involve a dynamic interplay of biological processes that result in spatially and temporally varying patterns of tissue formation and remodeling. For example, during bone fracture healing the cartilaginous callus that is formed initially in the fracture site is subsequently mineralized and remodeled to restore the original form and function to the injured bone. During much of this healing process, the fracture callus is comprised of a heterogeneous mixture of cartilage, fibrocartilage, multipotent mesenchymal tissue, and bone. Adding to this complexity, mechanical stimuli are known to influence the rate and type of tissues formed during skeletal healing [1]. Given the growing body of evidence that controlled mechanical stimulation may be used to enhance healing, it is of substantial interest to elucidate relationships between the distributions of local stresses and strains that develop within the healing region and the distribution of tissue types that form. While histomorphometry is a well established approach for characterizing the latter, it has historically been limited to analyses of a small number of two-dimensional sections of tissue. Such 2D sampling may be inadequate for quantitative characterization of the irregular geometry and heterogeneous composition of healing tissues. In this study, we report on a 3D histomorphometric method and apply this method to an in vivo model of skeletal repair [2] in which a bending stimulus delivered to a healing bone defect results in the formation of predominantly cartilage tissue, rather than bone.

Tissue Engineered Bone Using Polycaprolactone Scaffolds Made by Selective Laser Sintering

2004 ◽  
Vol 845 ◽  
Author(s):  
J. M. Williams ◽  
A. Adewunmi ◽  
R. M. Schek ◽  
C. L. Flanagan ◽  
P. H. Krebsbach ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Selective Laser Sintering ◽  
Mandibular Condyle ◽  
Computational Design ◽  
Laser Sintering ◽  
Histological Evaluation ◽  
Micro Computed Tomography ◽  
Element Analysis ◽  
Immunocompromised Mice

ABSTRACTPolycaprolactone is a bioresorbable polymer that has potential for tissue engineering of bone and cartilage. In this work, we report on the computational design and freeform fabrication of porous polycaprolactone scaffolds using selective laser sintering, a rapid prototyping technique. The microstructure and mechanical properties of the fabricated scaffolds were assessed and compared to designed porous architectures and computationally predicted properties. Compressive modulus and yield strength were within the lower range of reported properties for human trabecular bone. Finite element analysis showed that mechanical properties of scaffold designs and of fabricated scaffolds can be computationally predicted. Scaffolds were seeded with BMP-7 transduced fibroblasts and implanted subcutaneously in immunocompromised mice. Histological evaluation and micro-computed tomography (μCT) analysis confirmed that bone was generated in vivo. Finally, we have demonstrated the clinical application of this technology by producing a prototype mandibular condyle scaffold based on an actual pig condyle.

scholarly journals Longitudinal in vivo micro-CT-based approach allows spatio-temporal characterization of fracture healing patterns and assessment of biomaterials in mouse femur defect models

2020 ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C Tourolle né Betts ◽  
Gisela A Kuhn ◽  
Erica Floreani ◽  
Malavika H Nambiar ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Healing Process ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Collagen Scaffolds ◽  
Non Union ◽  
Spatio Temporal ◽  
Large Bone

AbstractThorough preclinical evaluation of novel biomaterials for treatment of large bone defects is essential prior to clinical application. Using in vivo micro-computed tomography (micro-CT) and mouse femoral defect models with different defect sizes, we were able to detect spatio-temporal healing patterns indicative of physiological and impaired healing in three defect sub-volumes and the adjacent cortex. The time-lapsed in vivo micro-CT-based approach was then applied to evaluate the bone regeneration potential of biomaterials using collagen and BMP-2 as test materials. Both collagen and BMP-2 treatment led to distinct changes in bone turnover in the different healing phases. Despite increased periosteal bone formation, 87.5% of the defects treated with collagen scaffolds resulted in non-unions. Additional BMP-2 application significantly accelerated the healing process and increased the union rate to 100%. This study further shows potential of time-lapsed in vivo micro-CT for capturing spatio-temporal deviations preceding non-union formation and how this can be prevented by application of biomaterials.This study therefore supports the application of longitudinal in vivo micro-CT for discrimination of normal and disturbed healing patterns and for the spatio-temporal characterization of the bone regeneration capacity of biomaterials.

scholarly journals Evaluation of longitudinal time-lapsedin vivomicro-CT for monitoring fracture healing in mouse femur defect models

2019 ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C Tourolle né Betts ◽  
Gisela A Kuhn ◽  
Ariane C Scheuren ◽  
Sandra Hofmann ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Radiation Effects ◽  
Callus Formation ◽  
Healing Process ◽  
Fracture Repair ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Healing Phase ◽  
Longitudinal Imaging

AbstractLongitudinalin vivomicro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0-6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching scheme (bridged vs. unbridged defect) combined with a two-threshold approach enabled assessment of localized bone turnover and mineralization kinetics relevant for monitoring callus remodeling. Weekly micro-CT application did not significantly change any of the assessed callus parameters in the defect and periosteal volumes. This was supported by histomorphometry showing only small amounts of cartilage residuals in both groups, indicating progression towards the end of the healing period. Also, immunohistochemical staining of Sclerostin, previously associated with mediating adverse radiation effects on bone, did not reveal differences between groups.The established longitudinalin vivomicro-CT-based approach allows monitoring of healing phases in mouse femur defect models without significant effects of anesthesia, handling and radiation on callus properties. Therefore, this study supports application of longitudinalin vivomicro-CT for healing-phase-specific monitoring of fracture repair in mice.

scholarly journals The mechanoresponse of bone is closely related to the osteocyte lacunocanalicular network architecture

2020 ◽  
Vol 117 (51) ◽  
pp. 32251-32259
Author(s):  
Alexander Franciscus van Tol ◽  
Victoria Schemenz ◽  
Wolfgang Wagermaier ◽  
Andreas Roschger ◽  
Hajar Razi ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Network Structure ◽  
Network Architecture ◽  
Local Strain ◽  
Bone Adaptation ◽  
Micro Computed Tomography ◽  
Entire Cross Section ◽  
Element Analysis ◽  
3D Network

Organisms rely on mechanosensing mechanisms to adapt to changes in their mechanical environment. Fluid-filled network structures not only ensure efficient transport but can also be employed for mechanosensation. The lacunocanalicular network (LCN) is a fluid-filled network structure, which pervades our bones and accommodates a cell network of osteocytes. For the mechanism of mechanosensation, it was hypothesized that load-induced fluid flow results in forces that can be sensed by the cells. We use a controlled in vivo loading experiment on murine tibiae to test this hypothesis, whereby the mechanoresponse was quantified experimentally by in vivo micro-computed tomography (µCT) in terms of formed and resorbed bone volume. By imaging the LCN using confocal microscopy in bone volumes covering the entire cross-section of mouse tibiae and by calculating the fluid flow in the three-dimensional (3D) network, we could perform a direct comparison between predictions based on fluid flow velocity and the experimentally measured mechanoresponse. While local strain distributions estimated by finite-element analysis incorrectly predicts preferred bone formation on the periosteal surface, we demonstrate that additional consideration of the LCN architecture not only corrects this erroneous bias in the prediction but also explains observed differences in the mechanosensitivity between the three investigated mice. We also identified the presence of vascular channels as an important mechanism to locally reduce fluid flow. Flow velocities increased for a convergent network structure where all of the flow is channeled into fewer canaliculi. We conclude that, besides mechanical loading, LCN architecture should be considered as a key determinant of bone adaptation.

scholarly journals The Role of Marine Organic Extract in Bone Regeneration: A Pilot Study

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
João César Zielak ◽  
Ivana Vendramini ◽  
Paola Fernanda Cotait de Lucas Corso ◽  
Leonardo Luiz Muller ◽  
Viviane Rozeira Crivellaro ◽  
...  
Keyword(s):  
Healing Process ◽  
Particle Sizes ◽  
Dependent Manner ◽  
Tissue Formation ◽  
Sheep Model ◽  
Organic Extract ◽  
Ethanoic Acid ◽  
Histological Results

Novel biomaterials capable of accelerating the healing process of skeletal tissues are urgently needed in dentistry. The present in vivo study assessed the osteoconductive and osteoinductive properties of experimental biphasic bioceramics (HA-TCP) modified or not by a nacre extract (marine organic extract, MOE) in a sheep model. Fabrication of MOE involved mixing ground nacre (0.05 g, particle sizes < 0.1 mm) with glacial ethanoic acid (5 mL, pH 7) for 72 hours using external magnetic stirring (25°C). Nonreactive carriers (sterile polythene tubes; 3/animal, radius: 2.5 mm, length: 10.0 mm) pertaining to the control (empty) or experimental groups (HA-TCP or MOE-modified HA-TCP) were implanted intramuscularly into the abdominal segment of the torso in sheep (n = 8, age: 2 years, weight: 45 kg). Euthanization of animals was performed at 3 and 6 months after surgery. Tissues harvested were subjected to macroscopic and radiographic assessments. Specimens were then stained for histological analysis. Both control and experimental animals were capable of inducing the neoformation of fibrous connective tissue at both time points where superior amounts of tissue formation and mineralization were detected for experimental groups (unaltered (at 3 and 6 mos) and MOE-modified HA-TCP (at 3 mos)). Histological results, however, revealed that mature bone formation was only observed for specimens fabricated with MOE-modified HA-TCP in a time-dependent manner. The present study has successfully demonstrated the in vivo utility of experimental biphasic bioceramics modified by MOE in an ectopic grafting sheep model. Promising osteoconductive and osteoinductive properties must be further developed and confirmed by subsequent research.

scholarly journals Spatio-temporal characterization of fracture healing patterns and assessment of biomaterials by time-lapsed in vivo micro-computed tomography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Esther Wehrle ◽  
Duncan C. Tourolle né Betts ◽  
Gisela A. Kuhn ◽  
Erica Floreani ◽  
Malavika H. Nambiar ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Bone Regeneration ◽  
Healing Process ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Collagen Scaffolds ◽  
Non Union ◽  
Spatio Temporal

AbstractThorough preclinical evaluation of functionalized biomaterials for treatment of large bone defects is essential prior to clinical application. Using in vivo micro-computed tomography (micro-CT) and mouse femoral defect models with different defect sizes, we were able to detect spatio-temporal healing patterns indicative of physiological and impaired healing in three defect sub-volumes and the adjacent cortex. The time-lapsed in vivo micro-CT-based approach was then applied to evaluate the bone regeneration potential of functionalized biomaterials using collagen and bone morphogenetic protein (BMP-2). Both collagen and BMP-2 treatment led to distinct changes in bone turnover in the different healing phases. Despite increased periosteal bone formation, 87.5% of the defects treated with collagen scaffolds resulted in non-unions. Additional BMP-2 application significantly accelerated the healing process and increased the union rate to 100%. This study further shows potential of time-lapsed in vivo micro-CT for capturing spatio-temporal deviations preceding non-union formation and how this can be prevented by application of functionalized biomaterials. This study therefore supports the application of longitudinal in vivo micro-CT for discrimination of normal and disturbed healing patterns and for the spatio-temporal characterization of the bone regeneration capacity of functionalized biomaterials.

scholarly journals Comparative skull biomechanics in Varanus and Salvator ‘Tupinambis’

2017 ◽  
Author(s):  
Hugo Dutel ◽  
Alana C Sharp ◽  
Marc E H Jones ◽  
Susan E Evans ◽  
Micheal J Fagan ◽  
...  
Keyword(s):  
Muscle Activity ◽  
Feeding Behaviour ◽  
Micro Computed Tomography ◽  
Lizard Species ◽  
Element Analysis ◽  
Joint Reaction Forces ◽  
Reaction Forces ◽  
Computer Based ◽  
Morphological Differences

The lizard species Salvator ‘Tupinambis’ merianae and Varanus ornatus evolved independently in South America and Africa but share similar ecology and feeding behaviour, despite having notable differences in their skull structure. Tupinambis has a compact, relatively short and wide snout, whereas that of Varanus is more slender and narrow. In addition, a postorbital bar (POB) is present in Tupinambis but absent in Varanus, and the former lacks the mid-frontal suture that is present in the latter. Here, we explore the biomechanical significance of these differences using 3D computer-based mechanical simulations based on micro-computed tomography, detailed muscle dissections, and in vivo data. First, we simulated muscle activity and joint-reaction forces during biting using Multibody Dynamics Analysis. Then, the forces calculated from these models were used as an input for Finite Element Analysis, to investigate and compare the strains of the skull in these two species. The effects of the presence/absence of structures, such as the POB, were investigated by constructing artificial models which geometry was altered. Our results indicate that strains in the skull bones are lower in Tupinambis than in Varanus, in particular at the back of the skull. The presence of a POB clearly reduces the strains in the bones during posterior biting in Tupinambis, but not in Varanus. Our results hence highlight how the morphological differences between these two taxa affect the mechanical behaviour of their respective skulls during feeding.

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