Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts.

Human cardiac organoids hold remarkable potential for cardiovascular disease modeling and human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) transplantation. Here, we show cardiac organoids engineered with electrically conductive silicon nanowires (e-SiNWs) significantly enhance the therapeutic efficacy of hPSC-CMs to treat infarcted hearts. We first demonstrated the biocompatibility of e-SiNWs and their capacity to improve cardiac microtissue engraftment in healthy rat myocardium.

Targeting HIF-α for robust prevascularization of human cardiac organoids.

Prevascularized 3D microtissues have been shown to be an effective cell delivery vehicle for cardiac repair. To this end, our lab has explored the development of self-organizing, prevascularized human cardiac organoids by co-seeding human cardiomyocytes with cardiac fibroblasts, endothelial cells, and stromal cells into agarose microwells. We hypothesized that this prevascularization process is facilitated by the endogenous upregulation of hypoxia-inducible factor (HIF) pathway in the avascular 3D microtissues.

Engineering a Chemically Defined Hydrogel Bioink for Direct Bioprinting of Microvasculature.

Vascularizing printed tissues is a critical challenge in bioprinting. While protein-based hydrogel bioinks have been successfully used to bioprint microvasculature, their compositions are ill-defined and subject to batch variation. Few studies have focused on engineering proangiogenic bioinks with defined properties to direct endogenous microvascular network formation after printing.

Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization.

Biologically active ligands (e.g., RGDS from fibronectin) play critical roles in the development of chemically defined biomaterials.

Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity.

Environmental factors are the largest contributors to cardiovascular disease. Here we show that cardiac organoids that incorporate an oxygen-diffusion gradient and that are stimulated with the neurotransmitter noradrenaline model the structure of the human heart after myocardial infarction (by mimicking the infarcted, border and remote zones), and recapitulate hallmarks of myocardial infarction (in particular, pathological metabolic shifts, fibrosis and calcium handling) at the transcriptomic, structural and functional levels. We also show that the organoids can model hypoxia-enhanced doxorubicin cardiotoxicity.

Transcriptomic analysis of short-term 17α-ethynylestradiol exposure in two Californian sentinel fish species sardine (Sardinops sagax) and mackerel (Scomber japonicus).

Endocrine disrupting chemicals (EDCs) are substances which disrupt normal functioning of the endocrine system by interfering with hormone regulated physiological pathways. Aquatic environments provide the ultimate reservoir for many EDCs as they enter rivers and the ocean via effluent discharges and accumulate in sediments. One EDC widely dispersed in municipal wastewater effluent discharges is 17α-ethynylestradiol (EE2), which is one of the most widely prescribed medicines.

De Novo Hepatic Transcriptome Assembly and Systems Level Analysis of Three Species of Dietary Fish, , , and .

The monitoring of marine species as sentinels for ecosystem health has long been a valuable tool worldwide, providing insight into how both anthropogenic pollution and naturally occurring phenomena (i.e., harmful algal blooms) may lead to human and animal dietary concerns.

Inspiration from heart development: Biomimetic development of functional human cardiac organoids.

Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions.

Development of peptide-functionalized synthetic hydrogel microarrays for stem cell and tissue engineering applications.

Unlabelled: Synthetic polymer microarray technology holds remarkable promise to rapidly identify suitable biomaterials for stem cell and tissue engineering applications. However, most of previous microarrayed synthetic polymers do not possess biological ligands (e.g.

Nanowires and Electrical Stimulation Synergistically Improve Functions of hiPSC Cardiac Spheroids.

The advancement of human induced pluripotent stem-cell-derived cardiomyocyte (hiPSC-CM) technology has shown promising potential to provide a patient-specific, regenerative cell therapy strategy to treat cardiovascular disease. Despite the progress, the unspecific, underdeveloped phenotype of hiPSC-CMs has shown arrhythmogenic risk and limited functional improvements after transplantation. To address this, tissue engineering strategies have utilized both exogenous and endogenous stimuli to accelerate the development of hiPSC-CMs.

Engineering alginate as bioink for bioprinting.

Recent advances in three-dimensional (3-D) printing offer an excellent opportunity to address critical challenges faced by current tissue engineering approaches. Alginate hydrogels have been used extensively as bioinks for 3-D bioprinting. However, most previous research has focused on native alginates with limited degradation.

3D printing facilitated scaffold-free tissue unit fabrication.

Tissue spheroids hold great potential in tissue engineering as building blocks to assemble into functional tissues. To date, agarose molds have been extensively used to facilitate fusion process of tissue spheroids. As a molding material, agarose typically requires low temperature plates for gelation and/or heated dispenser units.

3D Printing for Tissue Engineering.

Tissue engineering aims to fabricate functional tissue for applications in regenerative medicine and drug testing. More recently, 3D printing has shown great promise in tissue fabrication with a structural control from micro- to macro-scale by using a layer-by-layer approach. Whether through scaffold-based or scaffold-free approaches, the standard for 3D printed tissue engineering constructs is to provide a biomimetic structural environment that facilitates tissue formation and promotes host tissue integration (e.