4D Bioprinting Functional Cardiac Tissue
Description: Cardiovascular disease (CVD) associated with myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Traditional cell-based cardiac tissue regeneration methods show limited success in restoring cardiac function due to the immaturity of implanted cardiomyocytes. 4D printing is a highly innovative additive manufacturing process for fabricating pre-designed, self-assembly structures with a time-dependent dynamic change. The dynamic 4D effect of scaffolds may better replicate the behaviors of natural tissues to improve implanted cell maturation. The objective of this project is to create a highly innovative 4D bioprinted, vascularized cardiac tissue that replicates physiologically relevant mechanical loads for improving functional cardiomyocyte maturation. Two specific aims of this project are: (1) to synthesize and characterize novel 4D bioink materials. We will develop a biodegradable, near-infrared (NIR) light sensitive polyester bioink with precisely and remotely controlled 4D effects. The dynamic motion behavior of bioink material will be in-time controlled by switching the NIR light on/off, achieving heart-like contraction and relaxation. (2) to bioprint light responsive 4D vascularized cardiac constructs and investigate their regulation of myocardial functions. We will fabricate a 4D bioprinted anisotropic vascularized cardiac construct through coculture of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), endothelial cells, and cardiac fibroblasts. The 4D mechanical loading effect of the bioprinted cardiac tissue on iPSC-CM functional maturation and vascularization (capillary formation) will also be examined. We expect that innovatively integrating a 4D bioprinting platform with engineered cardiac constructs will create a physiologically relevant, functional cardiac tissue for MI treatment. Successful completion of the proposed work will provide the scientific community with a deeper understanding of how cardiomyocytes respond to dynamic mechanical stimulation in a 4D system, as well as the biomedical field with a revolutionary manufacturing technique. It will also address the clinical need for heart-on-chip models for pharmaceutical/toxicological screening and other potential applications.
Funder: American Heart Association
Amount: $300,000
Funding type: research
Funder scheme: Transformational Project Award
Start date: 2019-07-01
End date: 2022-06-30
Investigators: Lijie Zhang, Lijie Zhang
Institution: The George Washington University
Funded outputs count: 1
Funder award ID: 19TPA34850187
OpenAlex ID: G2803932367