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In vitro methods for evaluating therapeutic ultrasound exposures: present-day models and future innovations.

Alassaf A, Aleid A, Frenkel V - J Ther Ultrasound (2013)

Bottom Line: Each of these methods possesses characteristics that are well suited for various well-defined investigative goals.None, however, incorporate all the properties of real tissues, which include a 3D environment and live cells that may be maintained long-term post-treatment.Additional reporting is presented on the exciting and emerging field of 3D biological scaffolds, employing methods and materials adapted from tissue engineering.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Engineering, Catholic University of America, 620 Michigan Ave NE, Washington, DC 20064, USA.

ABSTRACT
Although preclinical experiments are ultimately required to evaluate new therapeutic ultrasound exposures and devices prior to clinical trials, in vitro experiments can play an important role in the developmental process. A variety of in vitro methods have been developed, where each of these has demonstrated their utility for various test purposes. These include inert tissue-mimicking phantoms, which can incorporate thermocouples or cells and ex vivo tissue. Cell-based methods have also been used, both in monolayer and suspension. More biologically relevant platforms have also shown utility, such as blood clots and collagen gels. Each of these methods possesses characteristics that are well suited for various well-defined investigative goals. None, however, incorporate all the properties of real tissues, which include a 3D environment and live cells that may be maintained long-term post-treatment. This review is intended to provide an overview of the existing application-specific in vitro methods available to therapeutic ultrasound investigators, highlighting their advantages and limitations. Additional reporting is presented on the exciting and emerging field of 3D biological scaffolds, employing methods and materials adapted from tissue engineering. This type of platform holds much promise for achieving more representative conditions of those found in vivo, especially important for the newest sphere of therapeutic applications, based on molecular changes that may be generated in response to non-destructive exposures.

No MeSH data available.


Related in: MedlinePlus

Experimental setups for ultrasound treatment of cultured cells. (a) The ultrasound transducer (T) is positioned directly below a culture well containing the cells (S). Acoustic gel is used to couple between the transducer and the well. (b) Degassed water is used to couple between the transducer and the sample. An ultrasound absorber (UA) is used to prevent the reflection of the ultrasound waves. (c) Similar to setup B however with a variation in orientation. (d) The ultrasound transducer is inserted into the well. This setup is typically used for small samples in 24- or 96-well plates (reprinted with permission from [29]).
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Figure 3: Experimental setups for ultrasound treatment of cultured cells. (a) The ultrasound transducer (T) is positioned directly below a culture well containing the cells (S). Acoustic gel is used to couple between the transducer and the well. (b) Degassed water is used to couple between the transducer and the sample. An ultrasound absorber (UA) is used to prevent the reflection of the ultrasound waves. (c) Similar to setup B however with a variation in orientation. (d) The ultrasound transducer is inserted into the well. This setup is typically used for small samples in 24- or 96-well plates (reprinted with permission from [29]).

Mentions: A comparatively large number of in vitro studies have been carried out investigating sonoporation (i.e., the use of ultrasound to generate pores to enhance drug and gene delivery to individual cells [34]). These include studies, for example, that use ultrasound contrast agents to enhance acoustic cavitation for this purpose [35]. These studies, typically carried out in a monolayer of cells, in open culture wells, typify the lack of suitability of these experimental setups for representing in vivo conditions. As will be described later in this review, one of the most important factors controlling cavitation activity is the geometry in which the bubble is confined [36]. The different possible experimental configurations for in vitro studies with cultured cells appear in FigureĀ 3.


In vitro methods for evaluating therapeutic ultrasound exposures: present-day models and future innovations.

Alassaf A, Aleid A, Frenkel V - J Ther Ultrasound (2013)

Experimental setups for ultrasound treatment of cultured cells. (a) The ultrasound transducer (T) is positioned directly below a culture well containing the cells (S). Acoustic gel is used to couple between the transducer and the well. (b) Degassed water is used to couple between the transducer and the sample. An ultrasound absorber (UA) is used to prevent the reflection of the ultrasound waves. (c) Similar to setup B however with a variation in orientation. (d) The ultrasound transducer is inserted into the well. This setup is typically used for small samples in 24- or 96-well plates (reprinted with permission from [29]).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109267&req=5

Figure 3: Experimental setups for ultrasound treatment of cultured cells. (a) The ultrasound transducer (T) is positioned directly below a culture well containing the cells (S). Acoustic gel is used to couple between the transducer and the well. (b) Degassed water is used to couple between the transducer and the sample. An ultrasound absorber (UA) is used to prevent the reflection of the ultrasound waves. (c) Similar to setup B however with a variation in orientation. (d) The ultrasound transducer is inserted into the well. This setup is typically used for small samples in 24- or 96-well plates (reprinted with permission from [29]).
Mentions: A comparatively large number of in vitro studies have been carried out investigating sonoporation (i.e., the use of ultrasound to generate pores to enhance drug and gene delivery to individual cells [34]). These include studies, for example, that use ultrasound contrast agents to enhance acoustic cavitation for this purpose [35]. These studies, typically carried out in a monolayer of cells, in open culture wells, typify the lack of suitability of these experimental setups for representing in vivo conditions. As will be described later in this review, one of the most important factors controlling cavitation activity is the geometry in which the bubble is confined [36]. The different possible experimental configurations for in vitro studies with cultured cells appear in FigureĀ 3.

Bottom Line: Each of these methods possesses characteristics that are well suited for various well-defined investigative goals.None, however, incorporate all the properties of real tissues, which include a 3D environment and live cells that may be maintained long-term post-treatment.Additional reporting is presented on the exciting and emerging field of 3D biological scaffolds, employing methods and materials adapted from tissue engineering.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Engineering, Catholic University of America, 620 Michigan Ave NE, Washington, DC 20064, USA.

ABSTRACT
Although preclinical experiments are ultimately required to evaluate new therapeutic ultrasound exposures and devices prior to clinical trials, in vitro experiments can play an important role in the developmental process. A variety of in vitro methods have been developed, where each of these has demonstrated their utility for various test purposes. These include inert tissue-mimicking phantoms, which can incorporate thermocouples or cells and ex vivo tissue. Cell-based methods have also been used, both in monolayer and suspension. More biologically relevant platforms have also shown utility, such as blood clots and collagen gels. Each of these methods possesses characteristics that are well suited for various well-defined investigative goals. None, however, incorporate all the properties of real tissues, which include a 3D environment and live cells that may be maintained long-term post-treatment. This review is intended to provide an overview of the existing application-specific in vitro methods available to therapeutic ultrasound investigators, highlighting their advantages and limitations. Additional reporting is presented on the exciting and emerging field of 3D biological scaffolds, employing methods and materials adapted from tissue engineering. This type of platform holds much promise for achieving more representative conditions of those found in vivo, especially important for the newest sphere of therapeutic applications, based on molecular changes that may be generated in response to non-destructive exposures.

No MeSH data available.


Related in: MedlinePlus