An official website of the United States government
Bioelectronic medicine is emerging as a powerful approach for restoring lost endogenous functions and addressing life-altering maladies such as cardiac disorders. Systems that incorporate both modulation of cellular function and recording capabilities can enhance the utility of these approaches and their customization to the needs of each patient. Here we report an integrated optogenetic and bioelectronic platform for stable and long-term stimulation and monitoring of cardiomyocyte function in vitro. Optical inputs are achieved through the expression of a photoactivatable adenylyl cyclase, that when irradiated with blue light causes a dose-dependent and time-limited increase in the secondary messenger cyclic adenosine monophosphate with subsequent rise in autonomous cardiomyocyte beating rate. Bioelectronic readouts are obtained through a multi-electrode array that measures real-time electrophysiological responses at 32 spatially-distinct locations. Irradiation at 27 μW mm−2 results in a 14% elevation of the beating rate within 20–25 min, which remains stable for at least 2 h. The beating rate can be cycled through “on” and “off” light states, and its magnitude is a monotonic function of irradiation intensity. The integrated platform can be extended to stretchable and flexible substrates, and can open new avenues in bioelectronic medicine, including closed-loop systems for cardiac regulation and intervention, for example, in the context of arrythmias.
more »
« less
An Integrated Optogenetic and Bioelectronic Platform for Regulating Cardiomyocyte Function
Abstract Bioelectronic medicine is emerging as a powerful approach for restoring lost endogenous functions and addressing life‐altering maladies such as cardiac disorders. Systems that incorporate both modulation of cellular function and recording capabilities can enhance the utility of these approaches and their customization to the needs of each patient. Here we report an integrated optogenetic and bioelectronic platform for stable and long‐term stimulation and monitoring of cardiomyocyte function in vitro. Optical inputs are achieved through the expression of a photoactivatable adenylyl cyclase, that when irradiated with blue light causes a dose‐dependent and time‐limited increase in the secondary messenger cyclic adenosine monophosphate with subsequent rise in autonomous cardiomyocyte beating rate. Bioelectronic readouts are obtained through a multi‐electrode array that measures real‐time electrophysiological responses at 32 spatially‐distinct locations. Irradiation at 27 µW mm−2results in a 14% elevation of the beating rate within 20–25 min, which remains stable for at least 2 h. The beating rate can be cycled through “on” and “off” light states, and its magnitude is a monotonic function of irradiation intensity. The integrated platform can be extended to stretchable and flexible substrates, and can open new avenues in bioelectronic medicine, including closed‐loop systems for cardiac regulation and intervention, for example, in the context of arrythmias.
more »
« less
- Award ID(s):
- 2239557
- PAR ID:
- 10641064
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Science
- Volume:
- 11
- Issue:
- 36
- ISSN:
- 2198-3844
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Electrical pacing/stimulations (EP) have been widely adopted to promote the maturation of hiPSC‐derived cardiomyocytes. However, there is a debate about their functions and effectiveness due to non‐optimized pacing conditions. Here, the effectiveness of EP (13 V cm−1, 2 ms in width, and 5 Hz frequency) on cardiac tissue beating mechanics are analyzed using digital image correlation (DIC). The cardiac tissues with and without EP at tissue culture time from day 2 to 11 (D2–D11) are characterized and compared. The results indicate EP decreased cardiac beating motion for ≈2–15 times, promote synchronization, and improve ion handling. A positive correlation between cardiac beating mechanics and ion handling is observed. DIC method can optimize chemical, mechanical, and electrical stimulation, which could help create more mature cardiac tissues.more » « less
-
Current methods for producing cardiomyocytes from human induced pluripotent stem cells (hiPSCs) using 2D monolayer differentiation are often hampered by batch-to-batch variability and inef!cient puri!cation processes. Here, we introduce CM-AI, a novel arti!cial intelligence-guided laser cell processing platform designed for rapid, label-free puri!cation of hiPSC-derived cardiomyocytes (hiPSC-CMs). This approach signi!cantly reduces processing time without the need for chronic metabolic selection or antibody-based sorting. By integrating real-time cellular morphology analysis and targeted laser ablation, CM-AI selectively removes non-cardiomyocyte populations with high precision. This streamlined process preserves cardiomyocyte viability and function, offering a scalable and ef!cient solution for cardiac regenerative medicine, disease modeling, and drug discomore » « less
-
Abstract Human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs) have emerged as an exciting new tool for cardiac research and can serve as a preclinical platform for drug development and disease modeling studies. However, these aspirations are limited by current culture methods in which hPSC‐CMs resemble fetal human cardiomyocytes in terms of structure and function. Herein we provide a novel in vitro platform that includes patterned extracellular matrix with physiological substrate stiffness and is amenable to both mechanical and electrical analysis. Micropatterned lanes promote the cellular and myofibril alignment of hPSC‐CMs while the addition of micropatterned bridges enable formation of a functional cardiac syncytium that beats synchronously over a large two‐dimensional area. We investigated the electrophysiological properties of the patterned cardiac constructs and showed they have anisotropic electrical impulse propagation, as occurs in the native myocardium, with speeds 2x faster in the primary direction of the pattern as compared to the transverse direction. Lastly, we interrogated the mechanical function of the pattern constructs and demonstrated the utility of this platform in recording the strength of cardiomyocyte contractions. This biomimetic platform with electrical and mechanical readout capabilities will enable the study of cardiac disease and the influence of pharmaceuticals and toxins on cardiomyocyte function. The platform also holds potential for high throughput evaluation of drug safety and efficacy, thus furthering our understanding of cardiovascular disease and increasing the translational use of hPSC‐CMs.more » « less
-
Abstract Cardiac microtissues provide a promising platform for disease modeling and developmental studies, which require the close monitoring of the multimodal excitation-contraction dynamics. However, no existing assessing tool can track these multimodal dynamics across the live tissue. We develop a tissue-like mesh bioelectronic system to track these multimodal dynamics. The mesh system has tissue-level softness and cell-level dimensions to enable stable embedment in the tissue. It is integrated with an array of graphene sensors, which uniquely converges both bioelectrical and biomechanical sensing functionalities in one device. The system achieves stable tracking of the excitation-contraction dynamics across the tissue and throughout the developmental process, offering comprehensive assessments for tissue maturation, drug effects, and disease modeling. It holds the promise to provide more accurate quantification of the functional, developmental, and pathophysiological states in cardiac tissues, creating an instrumental tool for improving tissue engineering and studies.more » « less
