The Spinebot—A Robotic Device to Intraoperatively Quantify Spinal Stiffness

Abstract Degenerative spine problems and spinal deformities have high socio-economic impacts. Current surgical treatment is based on bony fusion that can reduce mobility and function. Precise descriptions of the biomechanics of normal, deformed, and degenerated spinal segments under in vivo conditions are needed to develop new approaches that preserve spine function. This study developed a system that intraoperatively measures the three-dimensional segmental stiffness of patient's spine. SpineBot, a parallel kinematic robot, was developed to transmit loads to adjacent vertebrae. A force/torque load cell mounted on the SpineBot measured the moment applied to the spinal segment and calculated segmental stiffnesses. The accuracy of SpineBot was characterized ex vivo by comparing its stiffness measurement of five ovine specimens to measurements obtained with a reference spinal testing system. The SpineBot can apply torques up to 10 N·m along all anatomical axes with a total range of motion of about 11.5 deg ± 0.5 deg in lateral bending, 4.5 deg ± 0.3 deg in flexion/extension, and 2.6 deg ± 0.5 deg in axial rotation. SpineBot's measurements are noisier than the reference system, but the correlation between SpineBot and reference measurements was high (R2 > 0.8). In conclusion, SpineBot's accuracy is comparable to that of current reference systems but can take intraoperative measurements. SpineBot can improve our understanding of spinal biomechanics in patients who have the pathology of interest, and take these measurements in the natural physiological environment, giving us information essential to developing new “nonfusion” products.

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Fgfr2 is integral for bladder mesenchyme patterning and function

AJP Renal Physiology ◽

10.1152/ajprenal.00624.2014 ◽

2015 ◽

Vol 308 (8) ◽

pp. F888-F898 ◽

Cited By ~ 2

Author(s):

K. A. Walker ◽

Y. Ikeda ◽

I. Zabbarova ◽

C. M. Schaefer ◽

D. Bushnell ◽

...

Keyword(s):

Cell Fate ◽

Ex Vivo ◽

Smooth Muscle Actin ◽

Three Dimensional ◽

Growth Factor Receptor ◽

Immunoblot Analysis ◽

Type Ia ◽

And Function ◽

Passive Stretch

While urothelial signals, including sonic hedgehog (Shh), drive bladder mesenchyme differentiation, it is unclear which pathways within the mesenchyme are critical for its development. Studies have shown that fibroblast growth factor receptor (Fgfr)2 is necessary for kidney and ureter mesenchymal development. The objective of the present study was to determine the role of Fgfr2 in the bladder mesenchyme. We used Tbx18cre mice to delete Fgfr2 in the bladder mesenchyme ( Fgfr2 BM−/−). We performed three-dimensional reconstructions, quantitative real-time PCR, in situ hybridization, immunolabeling, ELISAs, immunoblot analysis, void stain on paper, ex vivo bladder sheet assays, and in vivo decerebrated cystometry. Compared with control bladders, embryonic day 16.5 (E16.5) Fgfr2 BM−/− bladders had thin muscle layers with less α-smooth muscle actin and thickened lamina propria with increased collagen type Ia and IIIa that intruded into the muscle. The reciprocal changes in mutant layer thicknesses appeared partly due to a cell fate switch. From postnatal days 1 to 30, Fgfr2 BM−/− bladders demonstrated progressive muscle loss and increased collagen expression. Postnatal Fgfr2 BM−/− bladder sheets exhibited decreased agonist-mediated contractility and increased passive stretch tension versus control bladder sheets. Cystometry revealed high baseline and threshold pressures and shortened intercontractile intervals in Fgfr2 BM−/− versus control bladders. Mechanistically, whereas Shh expression appeared normal, mRNA and protein readouts of hedgehog activity were increased in E16.5 Fgfr2 BM−/− versus control bladders. Moreover, E16.5 Fgfr2 BM−/− bladders exhibited higher levels of Cdo and Boc, hedgehog coreceptors that enhance sensitivity to Shh, compared with control bladders. In conclusion, loss of Fgfr2 in the bladder mesenchyme leads to abnormal bladder morphology and decreased compliance and contractility.

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Fgfr2 is integral for bladder mesenchyme patterning and function

AJP Renal Physiology ◽

10.1152/ajprenal.00463.2016 ◽

2017 ◽

Vol 312 (4) ◽

pp. F607-F618 ◽

Cited By ~ 4

Author(s):

Y. Ikeda ◽

I. Zabbarova ◽

C. M. Schaefer ◽

D. Bushnell ◽

W. C. De Groat ◽

...

Keyword(s):

Hedgehog Signaling ◽

Ex Vivo ◽

Smooth Muscle Actin ◽

Three Dimensional ◽

Growth Factor Receptor ◽

Collagen Expression ◽

And Function ◽

Passive Stretch

While urothelial signals, including sonic hedgehog (Shh), drive bladder mesenchyme differentiation, it is unclear which pathways within the mesenchyme are critical for its development. Studies have shown that fibroblast growth factor receptor 2 (Fgfr2) is necessary for kidney and ureter mesenchymal development. Our objective was to determine the role of Fgfr2 in bladder mesenchyme. We used Tbx18cre mice to delete Fgfr2 in bladder mesenchyme ( Fgfr2BM−/−). We performed three-dimensional reconstructions, quantitative real-time PCR, in situ hybridization, immunolabeling, ELISAs, immunoblotting, void stain on paper, ex vivo bladder sheet assays, and in vivo decerebrated cystometry. Compared with controls, embryonic ( E) day 16.5 ( E16.5) Fgfr2BM−/− bladders have thin muscle layers with reduced α-smooth muscle actin levels and thickened lamina propria with increased collagen expression that intrudes into muscle. From postnatal ( P) day 1 ( P1) to P30, Fgfr2BM−/− bladders demonstrate progressive muscle loss and increased collagen expression. Postnatal Fgfr2BM−/− bladder sheets exhibit decreased contractility and increased passive stretch tension compared with controls. In vivo cystometry revealed high baseline and threshold pressures and shortened intercontractile intervals in Fgfr2BM−/− bladders compared with controls. Mechanistically, while Shh expression appears normal, mRNA and protein readouts of hedgehog activity are increased in E16.5 Fgfr2BM−/− bladders compared with controls. Moreover, E16.5 Fgfr2BM−/− bladders exhibit higher levels of Cdo and Boc, hedgehog coreceptors that enhance sensitivity to Shh, than controls. Fgfr2 is critical for bladder mesenchyme patterning by virtue of its role in modulation of hedgehog signaling.

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Mice with cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks

Molecular Brain ◽

10.1186/s13041-021-00738-1 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

M. Asada-Utsugi ◽

K. Uemura ◽

M. Kubota ◽

Y. Noda ◽

Y. Tashiro ◽

...

Keyword(s):

Memory Function ◽

Three Dimensional ◽

Excitatory Synapses ◽

Missense Mutations ◽

Glutamatergic Synapses ◽

Learning Tasks ◽

Transmission Electron ◽

Nmdar Activation ◽

And Function

AbstractN-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2R714G, I715D, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 s than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.

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Performance of three-dimensional sonoelastography in prostate cancer detection: A comparison between ex vivo and in vivo experiments

2009 IEEE International Ultrasonics Symposium ◽

10.1109/ultsym.2009.5441763 ◽

2009 ◽

Cited By ~ 6

Author(s):

B. Castaneda ◽

K. Hoyt ◽

K. Westesson ◽

L. An ◽

J. Yao ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Detection ◽

Ex Vivo ◽

Three Dimensional ◽

Prostate Cancer Detection ◽

In Vivo Experiments

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hPSC-Derived Enteric Ganglioids Model Human ENS Development and Function

10.1101/2022.01.04.474746 ◽

2022 ◽

Author(s):

Homa Majd ◽

Ryan M Samuel ◽

Jonathan T Ramirez ◽

Ali Kalantari ◽

Kevin Barber ◽

...

Keyword(s):

Ex Vivo ◽

Xenograft Model ◽

Developmental Relationships ◽

Drug Candidates ◽

Effective Strategies ◽

Wide Range ◽

Functional Features ◽

And Function

The enteric nervous system (ENS) plays a central role in gut physiology and mediating the crosstalk between the gastrointestinal (GI) tract and other organs. The human ENS has remained elusive, highlighting the need for an in vitro modeling and mapping blueprint. Here we map out the developmental and functional features of the human ENS, by establishing robust and scalable 2D ENS cultures and 3D enteric ganglioids from human pluripotent stem cells (hPSCs). These models recapitulate the remarkable neuronal and glial diversity found in primary tissue and enable comprehensive molecular analyses that uncover functional and developmental relationships within these lineages. As a salient example of the power of this system, we performed in-depth characterization of enteric nitrergic neurons (NO neurons) which are implicated in a wide range of GI motility disorders. We conducted an unbiased screen and identified drug candidates that modulate the activity of NO neurons and demonstrated their potential in promoting motility in mouse colonic tissue ex vivo. We established a high-throughput strategy to define the developmental programs involved in NO neuron specification and discovered that PDGFR inhibition boosts the induction of NO neurons in enteric ganglioids. Transplantation of these ganglioids in the colon of NO neuron-deficient mice results in extensive tissue engraftment, providing a xenograft model for the study of human ENS in vivo and the development of cell-based therapies for neurodegenerative GI disorders. These studies provide a framework for deciphering fundamental features of the human ENS and designing effective strategies to treat enteric neuropathies.

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Kinematics and Laxity of Ulnohumeral Joint Under Valgus-Varus Stress

Journal of Musculoskeletal Research ◽

10.1142/s021895779800007x ◽

1998 ◽

Vol 02 (01) ◽

pp. 45-54 ◽

Cited By ~ 39

Author(s):

Shinji Tanaka ◽

Kai-Nan An ◽

Bernard F. Morrey

Keyword(s):

Elbow Joint ◽

Three Dimensional ◽

Elbow Flexion ◽

Axial Rotation ◽

Joint Laxity ◽

Treatment Modalities ◽

Trochlear Groove ◽

Flexion Extension ◽

Varus Stress ◽

Baseline Information

Three-dimensional kinematics of the ulnohumeral joint under simulated active elbow joint flexion-extension was obtained by using an electromagnetic tacking device. The joint motion was analyzed based on Eulerian angle description. In order to minimize the effect of "downstream cross-talk" on calculation of the three Eulerian angles, an optimal axis to best represent flexion-extension of the elbow joint was established. This axis, on average, is close to the line joining the centers of the capitellum and the trochlear groove. Furthermore, joint laxity under valgus-varus stress was also examined. With the weight of the forearm as the stress, maximums of 7.6° valgus-varus laxity and 5.3° axial rotation laxity were observed within a range of elbow flexion. The results of this study provide useful baseline information on joint laxity for the evaluation of elbow joints with implant replacements and other surgical treatment modalities.

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Three-Dimensional Cultures of Normal and Malignant Human Breast Epithelial Cells to Achieve in vivo-like Architecture and Function

Cell Biology ◽

10.1016/b978-012164730-8/50018-6 ◽

2006 ◽

pp. 139-149

Author(s):

C MYERS ◽

H LIU ◽

E LEE ◽

M BISSELL

Keyword(s):

Epithelial Cells ◽

Three Dimensional ◽

Human Breast ◽

Breast Epithelial Cells ◽

Breast Epithelial ◽

And Function ◽

Human Breast Epithelial Cells

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Decreased SLC26A3 expression and function in intestinal epithelial cells in response to Cryptosporidium parvum infection

AJP Cell Physiology ◽

10.1152/ajpcell.00278.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. C1205-C1212 ◽

Cited By ~ 2

Author(s):

Anoop Kumar ◽

Dulari Jayawardena ◽

Arivarasu N. Anbazhagan ◽

Ishita Chatterjee ◽

Shubha Priyamvada ◽

...

Keyword(s):

Epithelial Cells ◽

Cryptosporidium Parvum ◽

Diarrheal Disease ◽

Intestinal Epithelial Cells ◽

Ex Vivo ◽

Jejunal Mucosa ◽

Intestinal Epithelial ◽

Chloride Absorption ◽

And Function

The protozoan parasite Cryptosporidium parvum (CP) causes cryptosporidiosis, a diarrheal disease worldwide. Infection in immunocompetent hosts typically results in acute, self-limiting, or recurrent diarrhea. However, in immunocompromised individuals infection can cause fulminant diarrhea, extraintestinal manifestations, and death. To date, the mechanisms underlying CP-induced diarrheal pathogenesis are poorly understood. Diarrheal diseases most commonly involve increased secretion and/or decreased absorption of fluid and electrolytes. We and others have previously shown impaired chloride absorption in infectious diarrhea due to dysregulation of SLC26A3 [downregulated in adenoma (DRA)], the human intestinal apical membrane Cl−/[Formula: see text] exchanger protein. However, there are no studies on the effects of CP infection on DRA activity. Therefore, we examined the expression and function of DRA in intestinal epithelial cells in response to CP infection in vitro and in vivo. CP infection (0.5 × 106 oocysts/well in 24-well plates, 24 h) of Caco-2 cell monolayers significantly decreased Cl−/[Formula: see text] exchange activity (measured as DIDS-sensitive 125I uptake) as well as DRA mRNA and protein levels. Substantial downregulation of DRA mRNA and protein was also observed following CP infection ex vivo in mouse enteroid-derived monolayers and in vivo in the ileal and jejunal mucosa of C57BL/6 mice for 24 h. However, at 48 h after infection in vivo, the effects on DRA mRNA and protein were attenuated and at 5 days after infection DRA returned to normal levels. Our results suggest that impaired chloride absorption due to downregulation of DRA could be one of the contributing factors to CP-induced acute, self-limiting diarrhea in immunocompetent hosts.

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Biomechanical Analysis of Allograft Spacer Failure as a Function of Cortical-Cancellous Ratio in Anterior Cervical Discectomy/Fusion: Allograft Spacer Alone Model

Applied Sciences ◽

10.3390/app10186413 ◽

2020 ◽

Vol 10 (18) ◽

pp. 6413

Author(s):

Ji-Won Kwon ◽

Hwan-Mo Lee ◽

Tae-Hyun Park ◽

Sung Jae Lee ◽

Young-Woo Kwon ◽

...

Keyword(s):

Three Dimensional ◽

Element Model ◽

Axial Rotation ◽

Biomechanical Analysis ◽

Flexion Extension ◽

Hybrid Motion ◽

Anterior Cervical Discectomy Fusion ◽

Flexion And Extension ◽

Additional Fixation ◽

Lateral Walls

The design and ratio of the cortico-cancellous composition of allograft spacers are associated with graft-related problems, including subsidence and allograft spacer failure. Methods: The study analyzed stress distribution and risk of subsidence according to three types (cortical only, cortical cancellous, cortical lateral walls with a cancellous center bone) and three lengths (11, 12, 14 mm) of allograft spacers under the condition of hybrid motion control, including flexion, extension, axial rotation, and lateral bending,. A detailed finite element model of a previously validated, three-dimensional, intact C3–7 segment, with C5–6 segmental fusion using allograft spacers without fixation, was used in the present study. Findings: Among the three types of cervical allograft spacers evaluated, cortical lateral walls with a cancellous center bone exhibited the highest stress on the cortical bone of spacers, as well as the endplate around the posterior margin of the spacers. The likelihood of allograft spacer failure was highest for 14 mm spacers composed of cortical lateral walls with a cancellous center bone upon flexion (PVMS, 270.0 MPa; 250.2%) and extension (PVMS: 371.40 MPa, 344.2%). The likelihood of allograft spacer subsidence was also highest for the same spacers upon flexion (PVMS, 4.58 MPa; 28.1%) and extension (PVMS: 12.71 MPa, 78.0%). Conclusion: Cervical spacers with a smaller cortical component and of longer length can be risk factors for allograft spacer failure and subsidence, especially in flexion and extension. However, further study of additional fixation methods, such as anterior plates/screws and posterior screws, in an actual clinical setting is necessary.

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