Local tissue heterogeneity may modulate neuronal responses via altered axon strain fields: insights about innervated joint capsules from a computational model

Middendorf, Jill M.; Ita, Meagan E.; Winkelstein, Beth A.; Barocas, Victor H.

doi:10.1007/s10237-021-01506-9

Cited by 9 publications

(7 citation statements)

References 73 publications

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“…Further, it has been reported that cells sense load more intensely when attached to aligned fibers, which may lead to shifts in mechanotransduction [85]. Therefore, as cells produce aligned fibrils and fibers in our system, they may be sensing more load, which in the case of 5% cyclic load results in increased collagen production.…”

Section: Discussionmentioning

confidence: 89%

“…Another explanation for this temporal LOX activity may be a change in mechanotransduction with time in culture. We hypothesize that as our constructs mature from unorganized collagen to aligned fibrils, the cells within our constructs experience the loads differently and receive higher loads [85], ultimately altering their response to the load.…”

Section: Discussionmentioning

confidence: 99%

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Intermittent Cyclic Stretch of Engineered Ligaments Drives Hierarchical Collagen Fiber Maturation in a Dose- and Organizational-Dependent Manner

Troop,

Puetzer

2024

Preprint

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Hierarchical collagen fibers are the primary source of strength in tendons and ligaments, however these fibers do not regenerate after injury or with repair, resulting in limited treatment options. We previously developed a culture system that guides ACL fibroblasts to produce native-sized fibers and fascicles by 6 weeks. These constructs are promising ligament replacements, but further maturation is needed. Mechanical cues are critical for development in vivo and in engineered tissues; however, the effect on larger fiber and fascicle formation is largely unknown. Our objective was to investigate whether intermittent cyclic stretch, mimicking rapid muscle activity, drives further maturation in our system to create stronger engineered replacements and to explore whether cyclic loading has differential effects on cells at different degrees of collagen organization to better inform engineered tissue maturation protocols. Constructs were loaded with an established intermittent cyclic loading regime at 5 or 10% strain for up to 6 weeks and compared to static controls. Cyclic loading drove cells to increase hierarchical collagen organization, collagen crimp, and tissue mechanics, ultimately producing constructs that matched or exceeded immature ACL properties. Further, the effect of loading on cells varied depending on degree of organization. Specifically, 10% load drove early improvements in mechanics and composition, while 5% load was more beneficial later in culture, suggesting a cellular threshold response and a shift in mechanotransduction. This study provides new insight into how cyclic loading affects cell-driven hierarchical fiber formation and maturation, which will help to develop better rehabilitation protocols and engineer stronger replacements.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Intermittent Cyclic Stretch of Engineered Ligaments Drives Hierarchical Collagen Fiber Maturation in a Dose- and Organizational-Dependent Manner

Troop,

Puetzer

2024

Preprint

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“…Because subject‐specific structural information is not obtainable in vivo, this result points to a limitation of the proposed approach: the ability to describe detailed, small‐scale behavior of the tissue is limited by our ability to describe its small‐scale material properties. For instance, to study the effect of the macroscopic loading mechanisms on the local microscopic structural deformation surrounding a neuron in the ligament, a detailed structure‐based multiscale model would be needed 28,29,57 . If, however, the overall average strain in the ligament in different physiological motion is one's objective, then a simple NH model could generate an acceptable estimate of strain values.…”

Section: Discussionmentioning

confidence: 99%

“…One objective of FE models is to estimate the stresses and strains in the spinal tissues under various loading conditions since such measurements are difficult to make in experimental examinations. 23 , 24 , 25 , 26 , 27 The excessive predicted macroscopic stress and strain within the spinal tissues of such FE models can be used to determine the microscopic tension on the afferent fibers embedded in the FCL 28 , 29 and potentially can be associated to pain. Such FE models can ultimately facilitate the development of subject‐specific models that can be adopted as a complementary tool in clinical settings to advance prevention, diagnosis, and treatment plans in cervical injuries.…”

Section: Introductionmentioning

confidence: 99%

Cervical facet capsular ligament mechanics: Estimations based on subject‐specific anatomy and kinematics

et al. 2023

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BackgroundTo understand the facet capsular ligament's (FCL) role in cervical spine mechanics, the interactions between the FCL and other spinal components must be examined. One approach is to develop a subject‐specific finite element (FE) model of the lower cervical spine, simulating the motion segments and their components' behaviors under physiological loading conditions. This approach can be particularly attractive when a patient's anatomical and kinematic data are available.MethodsWe developed and demonstrated methodology to create 3D subject‐specific models of the lower cervical spine, with a focus on facet capsular ligament biomechanics. Displacement‐controlled boundary conditions were applied to the vertebrae using kinematics extracted from biplane videoradiography during planar head motions, including axial rotation, lateral bending, and flexion–extension. The FCL geometries were generated by fitting a surface over the estimated ligament–bone attachment regions. The fiber structure and material characteristics of the ligament tissue were extracted from available human cervical FCL data. The method was demonstrated by application to the cervical geometry and kinematics of a healthy 23‐year‐old female subject.ResultsFCL strain within the resulting subject‐specific model were subsequently compared to models with generic: (1) geometry, (2) kinematics, and (3) material properties to assess the effect of model specificity. Asymmetry in both the kinematics and the anatomy led to asymmetry in strain fields, highlighting the importance of patient‐specific models. We also found that the calculated strain field was largely independent of constitutive model and driven by vertebrae morphology and motion, but the stress field showed more constitutive‐equation‐dependence, as would be expected given the highly constrained motion of cervical FCLs.ConclusionsThe current study provides a methodology to create a subject‐specific model of the cervical spine that can be used to investigate various clinical questions by coupling experimental kinematics with multiscale computational models.

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“…Their contribution supports researchers from other fields of science and engineering who intend to move into the field of computational neuroscience and neuronal communications. Moreover, this field is less disconnected to standard artificial intelligence approaches and more linked to actual neuronal intelligence [ 33 , 34 , 35 , 36 , 37 ].…”

Section: Related Workmentioning

confidence: 99%

NeuronAlg: An Innovative Neuronal Computational Model for Immunofluorescence Image Segmentation

Giacopelli

Migliore

Tegolo

2023

Sensors

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Background: Image analysis applications in digital pathology include various methods for segmenting regions of interest. Their identification is one of the most complex steps and therefore of great interest for the study of robust methods that do not necessarily rely on a machine learning (ML) approach. Method: A fully automatic and optimized segmentation process for different datasets is a prerequisite for classifying and diagnosing indirect immunofluorescence (IIF) raw data. This study describes a deterministic computational neuroscience approach for identifying cells and nuclei. It is very different from the conventional neural network approaches but has an equivalent quantitative and qualitative performance, and it is also robust against adversative noise. The method is robust, based on formally correct functions, and does not suffer from having to be tuned on specific data sets. Results: This work demonstrates the robustness of the method against variability of parameters, such as image size, mode, and signal-to-noise ratio. We validated the method on three datasets (Neuroblastoma, NucleusSegData, and ISBI 2009 Dataset) using images annotated by independent medical doctors. Conclusions: The definition of deterministic and formally correct methods, from a functional and structural point of view, guarantees the achievement of optimized and functionally correct results. The excellent performance of our deterministic method (NeuronalAlg) in segmenting cells and nuclei from fluorescence images was measured with quantitative indicators and compared with those achieved by three published ML approaches.

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Local tissue heterogeneity may modulate neuronal responses via altered axon strain fields: insights about innervated joint capsules from a computational model

Cited by 9 publications

References 73 publications

Intermittent Cyclic Stretch of Engineered Ligaments Drives Hierarchical Collagen Fiber Maturation in a Dose- and Organizational-Dependent Manner

Intermittent Cyclic Stretch of Engineered Ligaments Drives Hierarchical Collagen Fiber Maturation in a Dose- and Organizational-Dependent Manner

Cervical facet capsular ligament mechanics: Estimations based on subject‐specific anatomy and kinematics

NeuronAlg: An Innovative Neuronal Computational Model for Immunofluorescence Image Segmentation

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