Research

Currently there are no therapies to effectively reverse cardiac injury following myocardial infarction. Tissue engineering holds promise for the regeneration of heart tissue through an engineered cardiac patch. Unfortunately, previous efforts have failed to achieve a cardiac patch with an effective engraftment rate and regenerative efficacy. The objective of this project is to biomimetically engineer an anisotropic cardiac patch containing an aligned cardiac tissue-specific nanofibrous extracellular matrix, dense and oriented capillary-like microvessels, and contractile human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This study represents a novel approach for engineering oriented capillary-like microvessels within 3D complex tissues, which will not only be used for regeneration of cardiac and other soft tissues, but also serve as a highly biomimetic vascular bed for disease modeling and drug screening.

Vascular grafts are in great demand due to the high occurrence of cardiovascular diseases. Despite the successful replacement of large-diameter blood vessels, small diameter blood vessels (such as coronary arteries) lack suitable replacement materials. Presently, no biomaterial or cell-based tissue-engineered vascular grafts can meet the urgent needs of patients for coronary artery substitutes. Although there has been great progress in developing cell sheet technology for tissue engineered vascular grafts, there is a striking deficit in our understanding of how the human cell donor characteristics influence the engineered material.  The objective of this project is to engineer, standardize, and optimize a mechanically strong extracellular matrix tube using a highly aligned nanofibrous scaffold and then combine it with an antithrombogenic cell type to biofabricate a mechanically strong off-the-shelf or personalized small-diameter tissue engineered vascular graft (TEVG).

 

The critical needs for wound coverage and healing have promoted the development of abundant commercial wound dressing products and skin substitutes. Although certain therapeutic effects have been achieved, critical limitations remain with these products. We aim to engineer an immune compatible and mechanically strong prevascularized skin dermis with highly organized interwoven extracellular matrix and vascular architecture, and evaluate the effects of the structured skin dermis on scar tissue reduction and wound healing promotion.

 

Secondary lymphedema is a lifelong and occasionally life-threatening disease that often occurs as a consequence of axillary clearance for breast cancer. Regeneration of lymphatic tissues and restoration of lymph flow through a fibrotic scar are two basic essentials for the treatment of secondary lymphedema. Human mesenchymal stem cells hold great therapeutic potential due to their effectiveness in stimulating host tissue regeneration via secreting numerous pro-regenerative factors dependent on the specific demands of the type and stage of injury. We utilize human mesenchymal stem cells to fabricate both cell sheet fragments as well as a completely biological tissue-engineered lymphatic collecting vessel, with the purpose to significantly reduce lymphatic edema and improve lymphatic regeneration via the in-site formation of functional lymphatic vasculature and the restoration of lymphatic drainage.

 

Graphical Abstract of published paper “Fibroblast-Generated Extracellular Matrix Guides Anastomosis during Wound Healing in an Engineered Lymphatic Skin Flap.”