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A cryoinjury model using engineered tissue equivalents for cryosurgical applications
Bumsoo Han1, Erin D Grassl, Victor H Barocas
1Department of Mechanical Engineering, University of Minnesota, 111 Church Street SE, Minneapolis, MN 55455, USA.
Abstract:
Cryosurgery is emerging as a promising treatment modality for various cancers, but there are still challenges to be addressed to improve its efficacy. Two primary challenges are determining thermal injury thresholds for various types of cell/tissue, and understanding of the mechanisms of freezing induced cell/tissue injury within a cryolesion. To address these challenges, various model systems ranging from cell suspensions to three-dimensional in vivo tissues have been developed and used. However, these models are either oversimplifications of in vivo tissues or difficult to control and extract precise experimental conditions from. Therefore, a more readily controllable model system with tissue-like characteristics is needed. In this study, a cryoinjury model was developed using tissue engineering technology, and the capabilities of the model were demonstrated. Engineered tissue equivalents (TEs) were constructed by seeding and culturing cells in a type I collagen matrix. Two different cell lines were used in this study, AT-1 rat prostate tumor cells and LNCaP human prostate cancer cells. The constructed TEs underwent a freeze/thaw cycle imitating in vivo cryosurgery. Thermal conditions within TEs during freeze/thaw cycles were characterized, and the responses of TEs to these thermal conditions including freezing induced cellular injury and extracellular matrix damage were investigated at three different time points. The results illustrate the feasibility to establish thermal thresholds of cryoinjury for different cell/tissue types using the presently developed model, and its potential capabilities to study cell death mechanisms, cell proliferation or migration, and extracellular matrix structural damage after a freeze/thaw cycle.
Insights
A novel tissue-engineered model using engineered tissue equivalents (TEs) allows for precise study of cryosurgery effects. This cryoinjury model helps determine thermal injury thresholds and understand freezing-induced cell damage in cancer treatment.
Area of Science:
- Biomedical Engineering
- Oncology
- Tissue Engineering
Background:
- Cryosurgery shows promise for cancer treatment but faces challenges in determining thermal injury thresholds and understanding freezing-induced cell damage.
- Current models for studying cryosurgery are either oversimplified or difficult to control, necessitating a more robust system.
- A readily controllable model with tissue-like characteristics is needed to advance cryosurgery research.
Purpose of the Study:
- To develop and validate a novel cryoinjury model using tissue engineering for cancer research.
- To assess the capabilities of engineered tissue equivalents (TEs) in mimicking in vivo cryosurgery conditions.
- To investigate thermal injury thresholds and cellular responses to freezing in a controlled, tissue-like environment.
Main Methods:
- Engineered tissue equivalents (TEs) were created by seeding AT-1 rat prostate tumor cells and LNCaP human prostate cancer cells in a type I collagen matrix.
- The TEs were subjected to a freeze/thaw cycle simulating in vivo cryosurgery.
- Thermal conditions, cellular injury, and extracellular matrix damage within the TEs were analyzed at three time points post-freezing.
Main Results:
- The study successfully demonstrated the feasibility of using engineered tissue equivalents (TEs) as a controllable cryoinjury model.
- Characterization of thermal conditions and investigation of cellular/extracellular matrix responses were performed.
- The model showed potential for establishing thermal thresholds for cryoinjury in different cell and tissue types.
Conclusions:
- The developed tissue-engineered cryoinjury model provides a controllable platform for studying cryosurgery efficacy.
- This model can be utilized to investigate mechanisms of cell death, proliferation, migration, and extracellular matrix damage after cryosurgery.
- Further research using this model can help optimize cryosurgical techniques for cancer treatment.
