Diffusion measurements in epidermal tissues with fluorescent recovery after photobleaching

Cornelissen, LH Lisette; Bronneberg, Debbie D; Oomens, Cwj Cees; Baaijens, Fpt Frank

doi:10.1111/j.1600-0846.2008.00313.x

Cited by 19 publications

(18 citation statements)

References 22 publications

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“…The relatively large difference in the value of the diffusion coefficient may result from the non-linear dependency of the diffusion coefficient on the molecular weight (Gu et al, 2004;Irrechukwu and Levenston, 2009). In addition, the difference may be reinforced by possible damage due to heat separation of the epidermis used by Cornelissen and co-workers (Cornelissen et al, 2008). The values for the dermis were comparable with the wide range of previously reported diffusion coefficient for relative small molecules in human dermis (190-300 Da) (Ibrahim and Kasting, 2010;Xing et al, 2009).…”

Section: Discussionsupporting

confidence: 85%

“…5). This value was considerably lower than 62 µm 2 /s , which had been previously measured in human epidermis using 20 kDa dextran (Cornelissen et al, 2008). The relatively large difference in the value of the diffusion coefficient may result from the non-linear dependency of the diffusion coefficient on the molecular weight (Gu et al, 2004;Irrechukwu and Levenston, 2009).…”

Section: Discussionmentioning

confidence: 54%

“…The diffusion coefficient for both the stratum corneum and air, and subcutaneous fat was always assigned a value of 0 µm 2 /s. The diffusion coefficient at different depths in the reticular dermis was determined first with the other layers assigned a value of 62 µm 2 /s, based on a previously reported diffusion coefficient for human epidermis (Cornelissen et al, 2008). The mean value determined from the four locations within the reticular dermis was then assigned to the reticular dermis and used to estimate the diffusion coefficient of the papillary dermis.…”

Section: Analysis Of the Diffusion Coefficient Using A Finite Elementmentioning

confidence: 99%

“…This parameter is essential to describe the passive transport of a molecule in a material and is dependent on both the properties of the diffusing molecule and the material through which it diffuses. In some previous studies, the diffusion coefficient of various model compounds in skin of different species was determined (Anissimov et al, 2012;Cornelissen et al, 2008;Hanh et al, 2001;Liu et al, 2013;Raphael et al, 2013;Wonglertnirant et al, 2010;Xing et al, 2009). Most of these studies report a single value of the diffusion coefficient for a single skin layer.…”

Section: Introductionmentioning

confidence: 99%

“…Most of these studies report a single value of the diffusion coefficient for a single skin layer. For example, Cornelissen et al (2008) measured the diffusion in human epidermis and Anissimov et al (2012) in the stratum corneum. However, the diffusion coefficient may not only vary between skin layers, but also within the layers of the skin.…”

Section: Introductionmentioning

confidence: 99%

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Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery

Römgens

Bader

Bouwstra

et al. 2015

Journal of the Mechanical Behavior of Biomedical Materials

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Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery, Journal of the Mechanical Behavior of Biomedical Materials, http://dx.doi. org/10.1016/j.jmbbm.2015.06.019 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractDelivering a drug into and through the skin is of interest as the skin can act as an alternative drug administration route for oral delivery. The development of new delivery methods, such as microneedles, makes it possible to not only deliver small molecules into the skin, which are able to pass the outer layer of the skin in therapeutic amounts, but also macromolecules. To provide insight into the administration of these molecules into the skin, the aim of this study was to assess the transport of macromolecules within and between its various layers. The diffusion coefficients in the epidermis and several locations in the papillary and reticular dermis were determined for fluorescein dextran of 40 and 500 kDa using a combination of fluorescent recovery after photobleaching experiments and finite element analysis. The diffusion coefficient was significantly higher for 40 kDa than 500 kDa dextran, with median values of 23 and 9 µm 2 /s in the dermis, respectively. The values only marginally varied within and between the papillary and reticular dermis. For the 40 kDa dextran, the diffusion coefficient in the epidermis was twice as low as in the dermis layers. The adopted method may be used for other macromolecules, which are of interest for dermal and transdermal drug delivery. The knowledge about diffusion in the skin is useful to optimize (trans)dermal drug delivery systems to target specific layers or cells in the human skin.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 54%

Section: Analysis Of the Diffusion Coefficient Using A Finite Elementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery

Römgens

Bader

Bouwstra

et al. 2015

Journal of the Mechanical Behavior of Biomedical Materials

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Microporous cell‐laden hydrogels for engineered tissue constructs

Park

Chung

Lee

et al. 2010

Biotech & Bioengineering

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In this paper, we describe an approach to generate microporous cell-laden hydrogels for fabricating biomimetic tissue engineered constructs. Micropores at different length scales were fabricated in cell-laden hydrogels by micromolding fluidic channels and leaching sucrose crystals. Microengineered channels were created within cell-laden hydrogel precursors that contained agarose solution mixed with sucrose crystals. The rapid cooling of the agarose solution was used to gel the solution and form micropores in place of the sucrose crystals. The sucrose leaching process generated micropores that were homogeneously distributed within the gels, while enabling the direct immobilization of cells within the gels. We also characterized the physical, mechanical, and biological properties (i.e. microporosity, diffusivity, and cell viability) of cell-laden agarose gels as a function of engineered porosity. The microporosity was controlled from 0% to 40% and the diffusivity of molecules in the porous agarose gels increased as compared to controls. Furthermore, the viability of human hepatocyte cells that were cultured in microporous agarose gels corresponded to the diffusion profile generated away from the microchannels. Based on their enhanced diffusive properties, microporous cell-laden hydrogels containing a microengineered fluidic channel could be a useful tool for generating tissue structures for regenerative medicine and drug discovery applications.

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Generation and evaluation of input values for computational analysis of transport processes within tissue cultures

Fattahi

Taheri

Schilling

et al. 2022

Engineering in Life Sciences

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Techniques for tissue culture have seen significant advances during the last decades and novel 3D cell culture systems have become available. To control their high complexity, experimental techniques and their Digital Twins (modelling and computational tools) are combined to link different variables to process conditions and critical process parameters. This allows a rapid evaluation of the expected product quality. However, the use of mathematical simulation and Digital Twins is critically dependent on the precise description of the problem and correct input parameters. Errors here can lead to dramatically wrong conclusions. The intention of this review is to provide an overview of the state‐of‐the‐art and remaining challenges with respect to generating input values for computational analysis of mass and momentum transport processes within tissue cultures. It gives an overview on relevant aspects of transport processes in tissue cultures as well as modelling and computational tools to tackle these problems. Further focus is on techniques used for the determination of cell‐specific parameters and characterization of culture systems, including sensors for on‐line determination of relevant parameters. In conclusion, tissue culture techniques are well‐established, and modelling tools are technically mature. New sensor technologies are on the way, especially for organ chips. The greatest remaining challenge seems to be the proper addressing and handling of input parameters required for mathematical models. Following Good Modelling Practice approaches when setting up and validating computational models is, therefore, essential to get to better estimations of the interesting complex processes inside organotypic tissue cultures in the future.

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Diffusion measurements in epidermal tissues with fluorescent recovery after photobleaching

Abstract: The diffusion could be measured in epidermal tissues using FRAP. In the future, the diffusion coefficients obtained in the current study will be used to study the difference between the transport in EpiDerm cultures and in human epidermis.

Cited by 19 publications

References 22 publications

Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery

Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery

Microporous cell‐laden hydrogels for engineered tissue constructs

Generation and evaluation of input values for computational analysis of transport processes within tissue cultures

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