Digital Light Processing 3D Printing Enables Versatile Fabrication of Human Engineered Heart Tissues

ABSTRACT: While cell models are routinely used to study cardiac molecular biology, in vitro systems fall far short of mimicking the metabolic and sarcomere structural maturity of intact cardiac tissue. Achieving a mature cardiomyocyte (CM) phenotype is essential for creating a physiologically relevant environment to accurately model and study cardiac diseases such as pathological hypertrophy. 3D in vitro engineered heart tissue (EHT) models recapitulate aspects of native cardiac physiology but are often limited in scalability and reproducibility, which poses a biological complexity-throughput conflict. Here, we report a simple, one-step method for rapid (on the order of minutes) fabrication of molds using digital light processing (DLP)-based 3D printing without the need for extensive multi-step processing. These DLP-printed molds support the controlled remodeling of extracellular matrix (ECM) hydrogels by human induced-pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to form EHTs with high reproducibility (>95% efficiency) and functional similarity across different batches of iPSC-CM differentiation. Further, the ease of design and stiffness/geometric flexibility afforded by DLP enables fabrication of EHTs with varying lengths, stiffnesses, and aspect ratios to control ECM composition and alignment. Additionally, this model shows expected enhanced metabolic and cytoskeletal maturity over 2D models and applicability for modeling pathological cellular processes associated with heart disease. Thus, our method, at the intersection of additive manufacturing and biomedicine, can aid in the development of robust yet simpler, cheaper, and more rapidly fabricated tissue models to study cardiac molecular biology in health and disease.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart, Pluripotent Stem Cell

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Christopher Ebmeier  

LAB HEAD: Leslie Anne Leinwand

PROVIDER: PXD074288 | Pride | 2026-09-21

REPOSITORIES: Pride