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  1. Article ; Online: MyoLoop: Design, development and validation of a standalone bioreactor for pathophysiological electromechanical in vitro cardiac studies.

    Pitoulis, Fotios G / Smith, Jacob J / Pamias-Lopez, Blanca / de Tombe, Pieter P / Hayman, Danika / Terracciano, Cesare M

    Experimental physiology

    2023  Volume 109, Issue 3, Page(s) 405–415

    Abstract: Mechanical load is one of the main determinants of cardiac structure and function. Mechanical load is studied in vitro using cardiac preparations together with loading protocols (e.g., auxotonic, isometric). However, such studies are often limited by ... ...

    Abstract Mechanical load is one of the main determinants of cardiac structure and function. Mechanical load is studied in vitro using cardiac preparations together with loading protocols (e.g., auxotonic, isometric). However, such studies are often limited by reductionist models and poorly simulated mechanical load profiles. This hinders the physiological relevance of findings. Living myocardial slices have been used to study load in vitro. Living myocardial slices (LMS) are 300-μm-thick intact organotypic preparations obtained from explanted animal or human hearts. They have preserved cellular populations and the functional, structural, metabolic and molecular profile of the tissue from which they are prepared. Using a three-element Windkessel (3EWK) model we previously showed that LMSs can be cultured while performing cardiac work loops with different preload and afterload. Under such conditions, LMSs remodel as a function of the mechanical load applied to them (physiological load, pressure or volume overload). These studies were conducted in commercially available length actuators that had to be extensively modified for culture experiments. In this paper, we demonstrate the design, development and validation of a novel device, MyoLoop. MyoLoop is a bioreactor that can pace, thermoregulate, acquire and process data, and chronically load LMSs and other cardiac tissues in vitro. In MyoLoop, load is parametrised using a 3EWK model, which can be used to recreate physiological and pathological work loops and the remodelling response to these. We believe MyoLoop is the next frontier in basic cardiovascular research enabling reductionist but physiologically relevant in vitro mechanical studies.
    MeSH term(s) Animals ; Humans ; Heart ; Bioreactors ; Myocardium ; Research Design
    Language English
    Publishing date 2023-10-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 1016295-1
    ISSN 1469-445X ; 0958-0670
    ISSN (online) 1469-445X
    ISSN 0958-0670
    DOI 10.1113/EP091247
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Smooth muscle cell contraction increases the critical buckling pressure of arteries.

    Hayman, Danika M / Zhang, Jinzhou / Liu, Qin / Xiao, Yangming / Han, Hai-Chao

    Journal of biomechanics

    2012  Volume 46, Issue 4, Page(s) 841–844

    Abstract: Recent in vitro experiments demonstrated that arteries under increased internal pressure or decreased axial stretch may buckle into the tortuous pattern that is commonly observed in aging or diseased arteries in vivo. It suggests that buckling is a ... ...

    Abstract Recent in vitro experiments demonstrated that arteries under increased internal pressure or decreased axial stretch may buckle into the tortuous pattern that is commonly observed in aging or diseased arteries in vivo. It suggests that buckling is a possible mechanism for the development of artery tortuosity. Vascular tone has significant effects on arterial mechanical properties but its effect on artery buckling is unknown. The objective of this study was to determine the effects of smooth muscle cell contraction on the critical buckling pressure of arteries. Porcine common carotid arteries were perfused in an ex vivo organ culture system overnight under physiological flow and pressure. The perfusion pressure was adjusted to determine the critical buckling pressure of these arteries at in vivo and reduced axial stretch ratios (1.5 and 1.3) at baseline and after smooth muscle contraction and relaxation stimulated by norepinephrine and sodium nitroprusside, respectively. Our results demonstrated that the critical buckling pressure was significantly higher when the smooth muscle was contracted compared with relaxed condition (97.3mmHg vs 72.9mmHg at axial stretch ratio of 1.3 and 93.7mmHg vs 58.6mmHg at 1.5, p<0.05). These results indicate that arterial smooth muscle cell contraction increased artery stability.
    MeSH term(s) Animals ; Arteries/drug effects ; Arteries/physiology ; Biomechanical Phenomena ; Blood Pressure/physiology ; Carotid Artery, Common/drug effects ; Carotid Artery, Common/physiology ; Muscle Contraction/drug effects ; Muscle Contraction/physiology ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/physiology ; Nitroprusside/pharmacology ; Norepinephrine/pharmacology ; Organ Culture Techniques ; Perfusion ; Sus scrofa ; Vasoconstriction/drug effects ; Vasoconstriction/physiology
    Chemical Substances Nitroprusside (169D1260KM) ; Norepinephrine (X4W3ENH1CV)
    Language English
    Publishing date 2012-12-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218076-5
    ISSN 1873-2380 ; 0021-9290
    ISSN (online) 1873-2380
    ISSN 0021-9290
    DOI 10.1016/j.jbiomech.2012.11.040
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Alterations in Pulse Pressure Affect Artery Function.

    Hayman, Danika M / Xiao, Yangming / Yao, Qingping / Jiang, Zonglai / Lindsey, Merry L / Han, Hai-Chao

    Cellular and molecular bioengineering

    2012  Volume 5, Issue 4, Page(s) 474–487

    Abstract: Pulse pressure changes in response to cardiovascular diseases and interventions, but its effect on vascular wall structure and function is poorly understood. We examined the effect of increased or decreased pulse pressure on artery function, cellular ... ...

    Abstract Pulse pressure changes in response to cardiovascular diseases and interventions, but its effect on vascular wall structure and function is poorly understood. We examined the effect of increased or decreased pulse pressure on artery function, cellular function, and extracellular matrix remodeling. Porcine carotid arteries were cultured under non-pulsatile (100 mmHg), pulsatile (70-130 mmHg), or hyper-pulsatile pressure (50-150 mmHg) for 1 to 3 days. Vasomotor response, wall permeability, cell proliferation, apoptosis, extracellular matrix remodeling, and proteins involved in atherogenesis were examined. Our results showed that hyper-pulsatile pressure decreased the artery response to sodium nitroprusside, basal tone, and wall permeability after three days. Non-pulsatile pressure increased cell proliferation. Neither hyper-pulsatile nor non-pulsatile pressure caused a change in the extracellular matrix or in the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, caveolin-1, or α-actin. Hyper-pulsatile pressure increased monocyte chemotactic protein-1 gene expression. Taken together, these changes indicate that pulse pressure has a limited effect on the artery immediately after its application. Specifically an increase in pulse pressure alters the artery tone and wall permeability while a decrease in pulse pressure alters cell proliferation. Overall these results provide insight into how the artery initially responds to changes in pulse pressure.
    Language English
    Publishing date 2012-12-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2416037-4
    ISSN 1865-5033 ; 1865-5025
    ISSN (online) 1865-5033
    ISSN 1865-5025
    DOI 10.1007/s12195-012-0251-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Alterations of pulse pressure stimulate arterial wall matrix remodeling.

    Yao, Qingping / Hayman, Danika M / Dai, Qiuxia / Lindsey, Merry L / Han, Hai-Chao

    Journal of biomechanical engineering

    2009  Volume 131, Issue 10, Page(s) 101011

    Abstract: The effect of pulse pressure on arterial wall remodeling has not been clearly defined. The objective of this study was to evaluate matrix remodeling in arteries under nonpulsatile and hyperpulsatile pressure as compared with arteries under normal ... ...

    Abstract The effect of pulse pressure on arterial wall remodeling has not been clearly defined. The objective of this study was to evaluate matrix remodeling in arteries under nonpulsatile and hyperpulsatile pressure as compared with arteries under normal pulsatile pressure. Porcine carotid arteries were cultured for 3 and 7 days under normal, nonpulsatile, and hyperpulsatile pressures with the same mean pressure and flow rate using an ex vivo organ culture model. Fenestrae in the internal elastic lamina, collagen, fibronectin, and gap junction protein connexin 43 were examined in these arteries using confocal microscopy, immunoblotting, and immunohistochemistry. Our results showed that after 7 days, the mean fenestrae size and the area fraction of fenestrae decreased significantly in nonpulsatile arteries (51% and 45%, respectively) and hyperpulsatile arteries (45% and 54%, respectively) when compared with normal pulsatile arteries. Fibronectin decreased (29.9%) in nonpulsatile arteries after 3 days but showed no change after 7 days, while collagen I levels increased significantly (106%) in hyperpulsatile arteries after 7 days. The expression of connexin 43 increased by 35.3% in hyperpulsatile arteries after 7 days but showed no difference in nonpulsatile arteries. In conclusion, our results demonstrated, for the first time, that an increase or a decrease in pulse pressure from its normal physiologic level stimulates structural changes in the arterial wall matrix. However, hyperpulsatile pressure has a more pronounced effect than the diminished pulse pressure. This effect helps to explain the correlation between increasing wall stiffness and increasing pulse pressure in vivo.
    MeSH term(s) Animals ; Blood Flow Velocity ; Blood Pressure ; Carotid Artery, Common/physiology ; Collagen Type I/metabolism ; Connexin 43/metabolism ; Elasticity ; Extracellular Matrix/metabolism ; Fibronectins/metabolism ; Immunohistochemistry ; Organ Culture Techniques ; Pulsatile Flow ; Swine ; Time Factors
    Chemical Substances Collagen Type I ; Connexin 43 ; Fibronectins
    Language English
    Publishing date 2009-10-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 243094-0
    ISSN 1528-8951 ; 0148-0731
    ISSN (online) 1528-8951
    ISSN 0148-0731
    DOI 10.1115/1.3202785
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The effects of isolation on chondrocyte gene expression.

    Hayman, Danika M / Blumberg, Todd J / Scott, C Corey / Athanasiou, Kyriacos A

    Tissue engineering

    2006  Volume 12, Issue 9, Page(s) 2573–2581

    Abstract: Tissue engineering of articular cartilage usually requires the isolation and culture of chondrocytes. Previous studies have suggested that enzymatic isolation may alter the metabolic activity and growth rate of chondrocytes. This study examined the ... ...

    Abstract Tissue engineering of articular cartilage usually requires the isolation and culture of chondrocytes. Previous studies have suggested that enzymatic isolation may alter the metabolic activity and growth rate of chondrocytes. This study examined the effects of 4 common isolation protocols on chondrocyte gene expression, morphology, and total cell yield immediately following the digest (t = 0) and after 2 culture periods (24 h and 1 week). Cartilage explants were digested using 1 of 4 protocols: (1) 6-h collagenase digest, (2) 22-h collagenase digest, (3) 45-min trypsin digest followed by a 3-h collagenase digest, or (4) 1.5-h pronase digest followed by a 3-h collagenase digest. Gene expression levels for glyceraldehyde-3-phosphate dehydrogenase, type I collagen, type II collagen, aggrecan, superficial zone protein, matrix metalloproteinase- 1, and tissue inhibitor of metalloproteinase-1 were measured at t = 0 h, 24 h, and 1 week using quantitative reverse transcriptase-polymerase chain reaction. In this study, cell yield was greatest for the 22-h collagenase and pronase-collagenase digests. However, the data indicate that a 6-h collagenase digest has the fewest gene expression changes compared to native cells. For tissue engineering, data from this study suggest that when cell yield is critical, a 22-h collagenase digest is preferable, but when obtaining cells closest to native chondrocytes is more desired, the 6-h collagenase digest is more beneficial.
    MeSH term(s) Animals ; Cartilage, Articular/cytology ; Cartilage, Articular/metabolism ; Cattle ; Cell Fractionation/methods ; Chondrocytes/cytology ; Collagenases/chemistry ; Gene Expression Profiling/methods ; Gene Expression Regulation ; Male ; Pronase/chemistry ; Time Factors ; Tissue Engineering/methods
    Chemical Substances Collagenases (EC 3.4.24.-) ; Pronase (EC 3.4.24.-)
    Language English
    Publishing date 2006-09
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1310000-2
    ISSN 1557-8690 ; 1076-3279
    ISSN (online) 1557-8690
    ISSN 1076-3279
    DOI 10.1089/ten.2006.12.2573
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The effect of static and dynamic loading on degradation of PLLA stent fibers.

    Hayman, Danika / Bergerson, Christie / Miller, Samantha / Moreno, Michael / Moore, James E

    Journal of biomechanical engineering

    2014  Volume 136, Issue 8

    Abstract: Understanding how polymers such as PLLA degrade in vivo will enhance biodegradable stent design. This study examined the effect of static and dynamic loads on PLLA stent fibers in vitro. The stent fibers (generously provided by TissueGen, Inc.) were ... ...

    Abstract Understanding how polymers such as PLLA degrade in vivo will enhance biodegradable stent design. This study examined the effect of static and dynamic loads on PLLA stent fibers in vitro. The stent fibers (generously provided by TissueGen, Inc.) were loaded axially with 0 N, 0.5 N, 1 N, or 0.125-0.25 N (dynamic group, 1 Hz) and degraded in PBS at 45 °C for an equivalent degradation time of 15 months. Degradation was quantified through changes in tensile mechanical properties. The mechanical behavior was characterized using the Knowles strain energy function and a degradation model. A nonsignificant increase in fiber stiffness was observed between 0 and 6 months followed by fiber softening thereafter. A marker of fiber softening, β, increased between 9 and 15 months in all groups. At 15 months, the β values in the dynamic group were significantly higher compared to the other groups. In addition, the model indicated that the degradation rate constant was smaller in the 1-N (0.257) and dynamic (0.283) groups compared to the 0.5-N (0.516) and 0-N (0.406) groups. While the shear modulus fluctuated throughout degradation, no significant differences were observed. Our results indicate that an increase in static load increased the degradation of mechanical properties and that the application of dynamic load further accelerated this degradation.
    MeSH term(s) Lactic Acid/chemistry ; Models, Theoretical ; Polyesters ; Polymers/chemistry ; Stents ; Stress, Mechanical ; Weight-Bearing
    Chemical Substances Polyesters ; Polymers ; Lactic Acid (33X04XA5AT) ; poly(lactide) (459TN2L5F5)
    Language English
    Publishing date 2014-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 243094-0
    ISSN 1528-8951 ; 0148-0731
    ISSN (online) 1528-8951
    ISSN 0148-0731
    DOI 10.1115/1.4027614
    Database MEDical Literature Analysis and Retrieval System OnLINE

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