skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on January 24, 2026

Title: Bioprinted optoelectronically active cardiac tissues
Electrical stimulation of existing three-dimensional bioprinted tissues to alter tissue activities is typically associated with wired delivery, invasive electrode placement, and potential cell damage, minimizing its efficacy in cardiac modulation. Here, we report an optoelectronically active scaffold based on printed gelatin methacryloyl embedded with micro-solar cells, seeded with cardiomyocytes to form light-stimulable tissues. This enables untethered, noninvasive, and damage-free optoelectronic stimulation–induced modulation of cardiac beating behaviors without needing wires or genetic modifications to the tissue solely with light. Pulsed light stimulation of human cardiomyocytes showed that the optoelectronically active scaffold could increase their beating rates (>40%), maintain high cell viability under light stimulation (>96%), and negligibly affect the electrocardiogram morphology. The seeded scaffolds, termed optoelectronically active tissues, were able to successfully accelerate heart beating in vivo in rats. Our work demonstrates a viable wireless, printable, and optically controllable tissue, suggesting a transformative step in future therapy of electrically active tissues/organs.  more » « less
Award ID(s):
2227063 2225698
PAR ID:
10569759
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more » ; ; ; ; ; « less
Publisher / Repository:
American Association for the Advancement of Science
Date Published:
Journal Name:
Science Advances
Volume:
11
Issue:
4
ISSN:
2375-2548
Page Range / eLocation ID:
adt7210
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. 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
  2. Untethered electrical stimulation or pacing of the heart is of critical importance in addressing the pressing needs of cardiovascular diseases in both clinical therapies and fundamental studies. Among various stimulation methods, light illumination–induced electrical stimulation via photoelectric effect without any genetic modifications to beating cells/tissues or whole heart has profound benefits. However, a critical bottleneck lies in the lack of a suitable material with tissue-like mechanical softness and deformability and sufficient optoelectronic performances toward effective stimulation. Here, we introduce an ultrathin (<500 nm), stretchy, and self-adhesive rubbery bio-optoelectronic stimulator (RBOES) in a bilayer construct of a rubbery semiconducting nanofilm and a transparent, stretchable gold nanomesh conductor. The RBOES could maintain its optoelectronic performance when it was stretched by 20%. The RBOES was validated to effectively accelerate the beating of the human induced pluripotent stem cell–derived cardiomyocytes. Furthermore, acceleration of ex vivo perfused rat hearts by optoelectronic stimulation with the self-adhered RBOES was achieved with repetitive pulsed light illumination. 
    more » « less
  3. null (Ed.)
    Hydrogels are a class of biomaterials used for a wide range of biomedical applications, including as a three-dimensional (3D) scaffold for cell culture that mimics the extracellular matrix (ECM) of native tissues. To understand the role of the ECM in the modulation of cardiac cell function, alginate was used to fabricate crosslinked gels with stiffness values that resembled embryonic (2.66 ± 0.84 kPa), physiologic (8.98 ± 1.29 kPa) and fibrotic (18.27 ± 3.17 kPa) cardiac tissues. The average pore diameter and hydrogel swelling were seen to decrease with increasing substrate stiffness. Cardiomyocytes cultured within soft embryonic gels demonstrated enhanced cell spreading, elongation, and network formation, while a progressive increase in gel stiffness diminished these behaviors. Cell viability decreased with increasing hydrogel stiffness. Furthermore, cells in fibrotic gels showed enhanced protein expression of the characteristic cardiac stress biomarker, Troponin-I, while reduced protein expression of the cardiac gap junction protein, Connexin-43, in comparison to cells within embryonic gels. The results from this study demonstrate the role that 3D substrate stiffness has on cardiac tissue formation and its implications in the development of complex matrix remodeling-based conditions, such as myocardial fibrosis. 
    more » « less
  4. Optogenetic methods for pacing of cardiac tissue can be realized by direct genetic modification of the cardiomyocytes to express light-sensitive actuators, such as channelrhodopsin-2, ChR2, or by introduction of light-sensitized non-myocytes that couple to the cardiac cells and yield responsiveness to optical pacing. In this study, we engineer three-dimensional “spark cells” spheroids, composed of ChR2-expressing human embryonic kidney cells (from 100 to 100,000 cells per spheroid), and characterize their morphology as function of cell density and time. These “spark-cell” spheroids are then deployed to demonstrate site-specific optical pacing of human stem-cell-derived cardiomyocytes (hiPSC-CMs) in 96-well format using non-localized light application and all-optical electrophysiology with voltage and calcium small-molecule dyes or genetically encoded sensors. We show that the spheroids can be handled using liquid pipetting and can confer optical responsiveness of cardiac tissue earlier than direct viral or liposomal genetic modification of the cardiomyocytes, with 24% providing reliable stimulation of the iPSC-CMs within 6 h and >80% within 24 h. Moreover, our data show that the spheroids can be frozen in liquid nitrogen for long-term storage and transportation, after which they can be deployed as a reagent on site for optical cardiac pacing. In all cases, optical stimulation was achieved at relatively low light levels (<0.15 mW/mm 2 ) when 5 ms or longer pulses were used. Our results demonstrate a scalable, cost-effective method with a cryopreservable reagent to achieve contactless optical stimulation of cardiac cell constructs without genetically modifying the myocytes, that can be integrated in a robotics-amenable workflow for high-throughput drug testing. 
    more » « less
  5. Abstract Tissue engineered cardiac patches have great potential as a regenerative therapy for myocardial infarction. Yet, the mutual interaction of cardiac patches with healthy tissue has not been completely understood. Here, we investigated the impact of acellular and cellular patches on a beating two-dimensional (2D) cardiac cell layer, and the effect of the beating of this layer on the cells encapsulated in the patch. We cultured human-induced pluripotent stem cell-derived cardiomyocytes (iCMs) on a coverslip and placed gelatin methacryloyl hydrogel alone or with encapsulated iCMs to create acellular and cellular patches, respectively. When the acellular patch was placed on the cardiac cell layer, the beating characteristics and Ca+2 handling properties reduced, whereas placing the cellular patch restored these characteristics. To better understand the effects of the cyclic contraction and relaxation induced by the beating cardiac cell layer on the patch placed on top of it, a simulation model was developed, and the calculated strain values were in agreement with the values measured experimentally. Moreover, this dynamic culture induced by the beating 2D iCM layer on the iCMs encapsulated in the cellular patch improved their beating velocity and frequency. Additionally, the encapsulated iCMs were observed to be coupled with the underlying beating 2D iCM layer. Overall, this study provides a detailed investigation on the mutual relationship of acellular/cellular patches with the beating 2D iCM layer, understanding of which would be valuable for developing more advanced cardiac patches. 
    more » « less