A toxicity cost function approach to optimal CPA equilibration in tissues

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Cryobiology

Background:

• Cryopreservation of tissues is vital for transplantation and regenerative medicine.
• Current cryopreservation methods lack uniformity and struggle with arbitrary tissue types.
• Computational models for tissue cryopreservation have historically been limited to explanatory approaches.

Purpose of the Study:

• To develop a numerical approach for optimizing tissue cryopreservation protocols.
• To adapt cell-based cryoprotective agent (CPA) equilibration damage models for tissue mass transport.
• To minimize cell-based cumulative toxicity and osmotic gradient damage during tissue cryopreservation.

Main Methods:

• Measured CPA (propylene glycol) diffusivity in human skin, fibroid, and myometrium tissues.
• Developed a numerical model integrating CPA diffusivity with tissue mass transport.
• Predicted and compared optimal multistep CPA equilibration protocols using computational simulations.

Main Results:

• Propylene glycol diffusivities were determined for skin (0.6 × 10⁻⁶ cm²/s), fibroid (1.2 × 10⁻⁶ cm²/s), and myometrium (1.3 × 10⁻⁶ cm²/s).
• Numerical predictions revealed distinct optimal protocols for minimizing CPA exposure time versus minimizing CPA toxicity.
• "One size fits all" stepwise protocols are predicted to be less efficient and more toxic than tailored approaches.

Conclusions:

• Tailored, multi-step CPA equilibration protocols are superior to uniform approaches for tissue cryopreservation.
• Computational modeling provides a powerful tool for optimizing cryopreservation strategies.
• This work advances the development of effective cryopreservation techniques for transplantation and regenerative medicine.