Drug‐induced cardiotoxicity is regarded as a major hurdle in the early stages of drug development. Although there are various methods for preclinical cardiotoxicity tests, they cannot completely predict the cardiotoxic potential of a compound due to the lack of physiological relevance. Recently, 3D engineered heart tissue (EHT) has been used to investigate cardiac muscle functions as well as pharmacological effects by exhibiting physiological auxotonic contractions. However, there is still no adequate platform for continuous monitoring to test acute and chronic pharmacological effects in vitro. Here, a biohybrid 3D printing method for fabricating a tissue‐sensor platform, composed of a bipillar‐grafted strain gauge sensor and EHT, is first introduced. Two pillars are three‐dimensionally printed as grafts onto a strain gauge‐embedded substrate to promote the EHT contractility and guide the self‐assembly of the EHTs along with the strain gauge. In addition, the integration of a wireless multi‐channel electronic system allows for continuous monitoring of the EHT contractile force by the tissue‐sensor platform and, ultimately, for the observation of the acute and chronic drug effects of cardiotoxicants. In summary, biohybrid 3D printing technology is expected to be a potential fabrication method to provide a next‐generation tissue‐sensor platform for an effective drug development process.
Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.
more » « less- PAR ID:
- 10225692
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 118
- Issue:
- 19
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- Article No. e2100077118
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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