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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

Nanoparticle uptake in type I collagen gels. pFUS exposures in the gels were provided at a single location, after which the gels were immersed in a suspension of 100-nm diameter, fluorescently labeled, polystyrene NPs. In all three gels (a, b, and c), the NPs were initially taken up only in the region of treatment. Even at 24 h later, the NPs were somewhat more diffuse but still found to be restricted to the treated region (VF, unpublished).
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Figure 2: Nanoparticle uptake in type I collagen gels. pFUS exposures in the gels were provided at a single location, after which the gels were immersed in a suspension of 100-nm diameter, fluorescently labeled, polystyrene NPs. In all three gels (a, b, and c), the NPs were initially taken up only in the region of treatment. Even at 24 h later, the NPs were somewhat more diffuse but still found to be restricted to the treated region (VF, unpublished).

Mentions: Collagen is another naturally occurring polymer in the body, whose structure can also affect the delivery of drugs [2]. Fibrillar collagen in the extracellular matrix of solid tumors, for example, can limit interstitial transport, preventing sufficient and uniform delivery of anticancer agents. This is especially true in the case of large agents such as viral gene delivery vectors whose size can be greater than the spaces between the fibers [24,25]. Studies on transport have been carried out in collagen type 1 gels, looking at permeability, diffusion, and convection for tracer molecules [26]. Similar collagen gels (the collagen being the same type found in the extracellular matrix of mammalian tissue) were used to investigate the effect of pFUS exposures on transport. The exposures were previously shown to generate gaps between parenchymal cells in animal models of both skeletal muscle [27] and solid tumors [28]. These structural changes increased the effective pore size of the tissue, resulting in enhanced convective mass transport of injected nanoparticles (NPs). The gels were given similar exposures and then immersed in the same fluorescently labeled NPs, 100 nm in diameter. Macroscopic fluorescent imaging showed the particles to initially be taken up only in the region of the focal zone. Twenty-four hours later, the NPs were still in the same region, where they were also shown to diffuse freely in the same gels without collagen (Figure 2). Similar to the effects reported previously in solid tumors [28], skeletal muscle [27], and blood clots [19,20], it is thought that the repetitive radiation force-induced displacements produced by the exposures may have created structural alterations; specifically the disruption of the organizational structure of the collagen fibers. As in the other studies, these effects could have potentially enabled improved transport through the gels (VF, unpublished).


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

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

Nanoparticle uptake in type I collagen gels. pFUS exposures in the gels were provided at a single location, after which the gels were immersed in a suspension of 100-nm diameter, fluorescently labeled, polystyrene NPs. In all three gels (a, b, and c), the NPs were initially taken up only in the region of treatment. Even at 24 h later, the NPs were somewhat more diffuse but still found to be restricted to the treated region (VF, unpublished).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Nanoparticle uptake in type I collagen gels. pFUS exposures in the gels were provided at a single location, after which the gels were immersed in a suspension of 100-nm diameter, fluorescently labeled, polystyrene NPs. In all three gels (a, b, and c), the NPs were initially taken up only in the region of treatment. Even at 24 h later, the NPs were somewhat more diffuse but still found to be restricted to the treated region (VF, unpublished).
Mentions: Collagen is another naturally occurring polymer in the body, whose structure can also affect the delivery of drugs [2]. Fibrillar collagen in the extracellular matrix of solid tumors, for example, can limit interstitial transport, preventing sufficient and uniform delivery of anticancer agents. This is especially true in the case of large agents such as viral gene delivery vectors whose size can be greater than the spaces between the fibers [24,25]. Studies on transport have been carried out in collagen type 1 gels, looking at permeability, diffusion, and convection for tracer molecules [26]. Similar collagen gels (the collagen being the same type found in the extracellular matrix of mammalian tissue) were used to investigate the effect of pFUS exposures on transport. The exposures were previously shown to generate gaps between parenchymal cells in animal models of both skeletal muscle [27] and solid tumors [28]. These structural changes increased the effective pore size of the tissue, resulting in enhanced convective mass transport of injected nanoparticles (NPs). The gels were given similar exposures and then immersed in the same fluorescently labeled NPs, 100 nm in diameter. Macroscopic fluorescent imaging showed the particles to initially be taken up only in the region of the focal zone. Twenty-four hours later, the NPs were still in the same region, where they were also shown to diffuse freely in the same gels without collagen (Figure 2). Similar to the effects reported previously in solid tumors [28], skeletal muscle [27], and blood clots [19,20], it is thought that the repetitive radiation force-induced displacements produced by the exposures may have created structural alterations; specifically the disruption of the organizational structure of the collagen fibers. As in the other studies, these effects could have potentially enabled improved transport through the gels (VF, unpublished).

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