A toxicity cost function approach to optimal CPA equilibration in tissues

James D. Benson, Adam Z. Higgins, Kunjan Desai, Ali Eroglu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

There is growing need for cryopreserved tissue samples that can be used in transplantation and regenerative medicine. While a number of specific tissue types have been successfully cryopreserved, this success is not general, and there is not a uniform approach to cryopreservation of arbitrary tissues. Additionally, while there are a number of long-established approaches towards optimizing cryoprotocols in single cell suspensions, and even plated cell monolayers, computational approaches in tissue cryopreservation have classically been limited to explanatory models. Here we develop a numerical approach to adapt cell-based CPA equilibration damage models for use in a classical tissue mass transport model. To implement this with real-world parameters, we measured CPA diffusivity in three human-sourced tissue types, skin, fibroid and myometrium, yielding propylene glycol diffusivities of 0.6 × 10−6 cm2/s, 1.2 × 10−6 cm2/s and 1.3 × 10−6 cm2/s, respectively. Based on these results, we numerically predict and compare optimal multistep equilibration protocols that minimize the cell-based cumulative toxicity cost function and the damage due to excessive osmotic gradients at the tissue boundary. Our numerical results show that there are fundamental differences between protocols designed to minimize total CPA exposure time in tissues and protocols designed to minimize accumulated CPA toxicity, and that “one size fits all” stepwise approaches are predicted to be more toxic and take considerably longer than needed.

Original languageEnglish (US)
Pages (from-to)144-155
Number of pages12
JournalCryobiology
Volume80
DOIs
StatePublished - Feb 1 2018

Fingerprint

Cost functions
Toxicity
Tissue
toxicity
Costs and Cost Analysis
Cryopreservation
diffusivity
cryopreservation
myometrium
Propylene Glycol
propylene glycol
Regenerative Medicine
tissues
Myometrium
Poisons
Leiomyoma
cells
mass transfer
skin (animal)
cell suspension culture

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

A toxicity cost function approach to optimal CPA equilibration in tissues. / Benson, James D.; Higgins, Adam Z.; Desai, Kunjan; Eroglu, Ali.

In: Cryobiology, Vol. 80, 01.02.2018, p. 144-155.

Research output: Contribution to journalArticle

Benson, James D. ; Higgins, Adam Z. ; Desai, Kunjan ; Eroglu, Ali. / A toxicity cost function approach to optimal CPA equilibration in tissues. In: Cryobiology. 2018 ; Vol. 80. pp. 144-155.
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