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Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening
Sangun Park1,2, Tae Hee Kim1, Soo Hyun Kim1,3
1Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
Abstract:
Recent advances in immunotherapies and molecularly targeted therapies have led to an increased interest in exploring the field of in vitro tumor mimetic platforms. An increasing need to understand the mechanisms of anti-cancer therapies has led to the development of natural tumor tissue-like in vitro platforms capable of simulating the tumor microenvironment. The incorporation of vascular structures into the in vitro platforms could be a crucial factor for functional investigation of most anti-cancer therapies, including immunotherapies, which are closely related to the circulatory system. Decellularized lung extracellular matrix (ldECM), comprised of ECM components and pro-angiogenic factors, can initiate vascularization and is ideal for mimicking the natural microenvironment. In this study, we used a ldECM-based hydrogel to develop a 3D vascularized lung cancer-on-a-chip (VLCC). We specifically encapsulated tri-cellular spheroids made from A549 cells, HUVECs, and human lung fibroblasts, for simulating solid type lung cancer. Additionally, two channels were incorporated in the hydrogel construct to mimic perfusable vessel structures that resemble arterioles or venules. Our study highlights how a more effective dose-dependent action of the anti-cancer drug Doxorubicin was observed using a VLCC over 2D screening. This observation confirmed the potential of the VLCC as a 3D in vitro drug screening tool.
Insights
Researchers developed a 3D vascularized lung cancer-on-a-chip (VLCC) using decellularized lung extracellular matrix. This platform demonstrated enhanced Doxorubicin drug screening efficacy compared to traditional 2D methods.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Drug Discovery
Background:
- Advances in cancer immunotherapies and targeted therapies necessitate better in vitro models.
- Simulating the tumor microenvironment, including vascularization, is crucial for understanding anti-cancer drug mechanisms.
- Decellularized lung extracellular matrix (ldECM) provides a natural scaffold for vascularization and microenvironment mimicry.
Purpose of the Study:
- To develop a 3D vascularized lung cancer-on-a-chip (VLCC) model.
- To investigate the potential of ldECM-based hydrogels for creating perfusable vascular structures.
- To evaluate the VLCC as a platform for anti-cancer drug screening.
Main Methods:
- Fabrication of an ldECM-based hydrogel.
- Encapsulation of tri-cellular spheroids (A549 cells, HUVECs, human lung fibroblasts) within the hydrogel.
- Incorporation of perfusable microchannels to mimic vascular structures.
- Assessment of Doxorubicin efficacy using the VLCC compared to 2D screening.
Main Results:
- Successful development of a 3D VLCC model mimicking solid lung cancer.
- Demonstration of perfusable vessel-like channels within the hydrogel construct.
- Observed a more effective dose-dependent action of Doxorubicin using the VLCC compared to 2D screening.
Conclusions:
- The VLCC serves as a promising 3D in vitro model for simulating lung cancer.
- The ldECM-based hydrogel effectively supports vascularization and microenvironment mimicry.
- The VLCC platform shows significant potential for improved 3D in vitro drug screening of anti-cancer therapies.
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